Film Formation of High Tg Latex Using Hydroplasticization: Explanations from NMR Relaxometry
Voogt, Benjamin ; Huinink, Hendrik P. ; Erich, Sebastiaan J.F. ; Scheerder, Jurgen ; Venema, Paul ; Keddie, Joseph L. ; Adan, Olaf C.G. - \ 2019
Langmuir 35 (2019)38. - ISSN 0743-7463 - p. 12418 - 12427.
The film formation of acrylic latex dispersions, containing different amounts of carboxylic acid functional groups by the incorporation of methacrylic acid (MAA), was studied with GARField 1H NMR at various relative humidities (RH). Polymer particles with glass-transition temperatures in the range from 26 to 50 °C formed films at room temperature because of hydroplasticization. It was found that with an increased drying rate due to lower RH, the evaporation flux of water was limited by the latex polymer. Only in the second stage of drying this phenomenon was more obvious with increasing MAA content. 1H NMR relaxometry was used to study the change of hydrogen mobilities during film formation and hardening of the films. This showed that the drying rate itself had no impact on the hydrogen mobility in the latex films as measured via the T2 relaxation time. Hydrogen mobilities of water and the mobile polymer phase only significantly decrease after most water has evaporated. This implies that the rigidity of the polymers increases with the evaporation of water that otherwise plasticizes the polymer through hydrogen bonding with the carboxylic acid groups. This hardening of the polymer phase is essential for applications in a coating. The hydrogen mobilities were affected by the MAA concentration. Densities of mobile hydrogens increase with increasing MAA content. This is expected if the mobile protons are contained in the MAA groups. The result thus confirms the role of carboxylic acid groups in hydrogen bonding and plasticization of the copolymers. Hydrogen mobilities, however, decrease with increasing MAA content, which is hypothesized to be caused by the formation of dimers of carboxylic acid groups that still hold water. They still enable short-range polymer hydrogen mobility due to hydroplasticization but limit long-range polymer mobility due to interaction between the carboxylic acid groups.
Surface characterization of drying acrylic latex dispersions with variable methacrylic acid content using surface dilatational rheology
Voogt, Benjamin ; Venema, Paul ; Sagis, Leonard ; Huinink, Henk ; Erich, Bart ; Scheerder, Jurgen ; Adan, Olaf - \ 2019
Journal of Colloid and Interface Science 556 (2019). - ISSN 0021-9797 - p. 584 - 591.
Dilatational rheology - Drying - Interface - Latex - Methacrylic acid
Hypothesis: Drying of latex dispersions often results in particle gradients at the latex-air interface. We expect that, by increasing the carboxylic acid content of latex particles, inter-particle interactions at the interface change. With dilatational rheology one could detect particle-particle interactions in an early stage of the drying process and elucidate the nature of these interactions. Experiments: Acrylic latex dispersions were prepared with different amounts of methacrylic acid (MAA), ranging from 2 to 10 wt% on dry mass. Dilatational rheology studies during drying at different relative humidities RH were performed using profile analysis tensiometry. Visco-elastic properties of latex surfaces were used to identify inter-particle interactions at the surfaces depending on the drying rate and particle composition. Findings: Drying at 85% RH did not show significant changes of the mechanical properties of the latex surfaces. Drying at 65 and 53% RH resulted in a change of the mechanical properties, ultimately showing non-linear visco-elastic behavior. This indicates that capillary and/or Van der Waals forces were operating between particles at the surface. With increasing MAA content the viscous contribution decreased, possibly due to the formation of more gel-like structures at the particle surface due to higher solubility of polymer segments near to the surface.
Development and body mass inversely affect children's brain activation in dorsolateral prefrontal cortex during food choice
Meer, Floor van; Laan, Laura N. van der; Eiben, Gabriele ; Lissner, Lauren ; Wolters, Maike ; Rach, Stefan ; Herrmann, Manfred ; Erhard, Peter ; Molnar, Denes ; Orsi, Gergely ; Viergever, Max A. ; Adan, Roger A.H. ; Smeets, Paul A.M. - \ 2019
NeuroImage 201 (2019). - ISSN 1053-8119
Decision making - Development - fMRI - Food choice - Overweight
Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.
Seminal plasma amino acid profile in different breeds of chicken : Role of seminal plasma on sperm cryoresistance
Santiago-Moreno, Julián ; Bernal, Berenice ; Pérez-Cerezales, Serafín ; Castaño, Cristina ; Toledano-Díaz, Adolfo ; Esteso, Milagros C. ; Gutiérrez-Adán, Alfonso ; López-Sebastián, Antonio ; Gil, María G. ; Woelders, Henri ; Blesbois, Elisabeth - \ 2019
PLoS ONE 14 (2019)1. - ISSN 1932-6203
Seminal plasma is a key biological fluid that modulates sperm function in the reproduction process. However, its role in sperm biotechnologies is scarce in poultry. The aims of the present study were to study the amino acids profile and total proteins of seminal plasma in 12 Spanish chicken breeds and to investigate the role of seminal plasma on cryoresistance of rooster sperm. To investigate the role of seminal plasma on cryoresistance, diluted pooled semen samples were cryopreserved in the presence and absence of seminal plasma. Glutamic acid was the most abundant free amino acid in seminal plasma, followed by alanine, serine, valine, and glycine. There was an influence of breed (P<0.05) on the percentage of viable sperm after freezing-thawing of samples with seminal plasma. Cluster analysis revealed that White Prat, Black Castellana, Blue Andaluza, Quail Castellana, and Red-Barred Vasca returned the best freezing-thawing response (good freezers). There was a positive correlation between seminal plasma concentrations of valine, isoleucine lysine, leucine and post thaw viability. The evaluation of fertilization capacity of frozen-thawed semen from the breeds White Prat (‘good freezer’) and Black-Red Andaluza (‘bad freezer’) showed that good freezer had higher fertility (20/68, 29.4%) compared to bad freezer breed (14/76, 18.4%), even if the difference was not significant (P = 0.08). The TUNEL assay revealed that freezing/thawing procedures in presence of seminal plasma provoked higher DNA fragmentation in most of the breeds, with a positive correlation between seminal alanine, valine, isoleucine, methionine, leucine, tyrosine, phenylalanine concentrations and DNA integrity. DNA fragmentation was lower in absence of seminal plasma and the breed effect on sperm viability was highly reduced. It is concluded that specific seminal plasma amino acids were associated with post-thaw percentage of viable sperm and DNA integrity. The removal of seminal plasma decreases the variability of the results and DNA fragmentation damages.
Water mobility during drying of hard and soft type latex : Systematic GARField 1H NMR relaxometry studies
Voogt, Benjamin ; Huinink, Henk ; Erich, Bart ; Scheerder, Jurgen ; Venema, Paul ; Adan, Olaf - \ 2018
Progress in Organic Coatings 123 (2018). - ISSN 0300-9440 - p. 111 - 119.
GARField H NMR - Latex drying - Relaxometry - T - Water mobility
GARField 1H NMR relaxometry experiments were done to study the drying process of two latices with different polymer Tg and to elucidate water mobility behavior during this process. It was found that the hard type latex, with a polymer Tg above room temperature, dries faster than the soft type latex, with a polymer Tg below room temperature. Diffusion measurements by means of echo time variations at different moments in the drying process show that water auto-diffusion decreases with increasing solid content of the latex independent of particle Tg. Two pools of protons with different mobilities were observed based on transversal relaxation T2. Determination of the long T2,long's and short T2,short's of both latex dispersions and their respective proton densities during drying at 80% RH showed evidence of particle deformation for the soft type latex and the absence thereof for the hard type latex. Additional drying of the resulting coatings with anhydrous CaCl2 showed a higher porosity for the hard type coating based on the proton distribution profile width. Moreover, two domains with different polymer proton mobilities are found for both coatings that are both plasticized by water at 80% RH. This is more apparent for the hard type coating, suggesting that a more hydrophilic polymer gives a higher degree of plasticization.
Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults
Meer, Floor van; Laan, Laura N. van der; Viergever, Max A. ; Adan, Roger A.H. ; Smeets, Paul A.M. - \ 2017
NeuroImage 159 (2017). - ISSN 1053-8119 - p. 325 - 333.
Children - Decision making - Development - fMRI - Food choice
Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is involved in self-control. We aimed to examine the neural correlates of food choice in children, and how considering healthiness affects neural activity and choice behavior. 24 children and 28 adults performed a food choice task while being scanned with fMRI and provided health and taste ratings of the foods afterwards. During the choice task participants considered either the healthiness or tastiness of the food or chose naturally. Health rating was a positive predictor of choice in adults, but a negative predictor in children. Children had weaker dlPFC activation than adults during yes vs. no independent of health or taste condition. Both children and adults made healthier choices when considering healthiness. Taste rating modulated mPFC activation in both children and adults. When considering the healthiness, health rating positively modulated mPFC activation in adults, but negatively in children. Considering the healthiness increased connectivity between dlPFC and mPFC in adults, but not in children. In conclusion, considering healthiness can promote healthier choices in both children and adults, but is accompanied by an opposing pattern of brain activation in the mPFC. Since the absolute number of healthy choices remained lower in children, this suggests that children may not yet be geared to modify their choices away from their natural tendency to choose unhealthy tasty foods. Thus, this study suggests that it may be promising to develop interventions that increase children's preference for healthy food, for example by increasing the habitual consumption of healthy foods from a young age.
The determinants of food choice
Leng, Gareth ; Adan, Roger A.H. ; Belot, Michele ; Brunstrom, Jeffrey M. ; Graaf, Kees de; Smeets, Paul A.M. - \ 2017
Proceedings of the Nutrition Society 76 (2017)3. - ISSN 0029-6651 - p. 316 - 327.
Appetite - Brain imaging - Food choice - Hypothalamus - Policy - Satiety
Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.
Developmental differences in the brain response to unhealthy food cues : An fMRI study of children and adults
Meer, Floor van; Laan, Laura N. van der; Charbonnier, Lisette ; Viergever, Max A. ; Adan, Roger A.H. ; Smeets, Paul A.M. - \ 2016
American Journal of Clinical Nutrition 104 (2016)6. - ISSN 0002-9165 - p. 1515 - 1522.
Childhood obesity - Children - FMRI - Food viewing - Healthy food
Background: Food cues are omnipresent and may trigger overconsumption. In the past 2 decades, the prevalence of childhood obesity has increased dramatically. Because children's brains are still developing, especially in areas important for inhibition, children may be more susceptible than adults to tempting food cues. Objective: We examined potential developmental differences in children's and adults' responses to food cues to determine how these responses relate to weight status. Design: We included 27 children aged 10-12 y and 32 adults aged 32-52 y. Functional magnetic resonance imaging data were acquired during a food-viewing task in which unhealthy and healthy food pictures were presented. Results: Children had a stronger activation in the left precentral gyrus than did adults in response to unhealthy compared with healthy foods. In children, unhealthy foods elicited stronger activation in the right inferior temporal and middle occipital gyri, left precentral gyrus, bilateral opercular part of the inferior frontal gyrus, left hippocampus, and left middle frontal gyrus. Adults had stronger activation in the bilateral middle occipital gyrus and the right calcarine sulcus for unhealthy compared with healthy foods. Children with a higher body mass index (BMI) had lower activation in the bilateral dorsolateral prefrontal cortex while viewing unhealthy compared with healthy foods. In adults there was no correlation between BMI and neural response to unhealthy compared with healthy foods. Conclusions: Unhealthy foods might elicit more attention both in children and in adults. Children had stronger activation while viewing unhealthy compared with healthy foods in areas involved in reward, motivation, and memory. Furthermore, children activated a motivation and reward area located in the motor cortex more strongly than did adults in response to unhealthy foods. Finally, children with a higher BMI had less activation in inhibitory areas in response to unhealthy foods, which may mean they are more susceptible to tempting food cues.
Associations between neural correlates of visual stimulus processing and set-shifting in ill and recovered women with anorexia nervosa
Sultson, Hedvig ; Meer, Floor van; Sanders, Nicole ; Elburg, Annemarie A. van; Danner, Unna N. ; Hoek, Hans W. ; Adan, Roger A.H. ; Smeets, Paul A.M. - \ 2016
Psychiatry Research - Neuroimaging 255 (2016). - ISSN 0925-4927 - p. 35 - 42.
Cognitive inflexibility - Food viewing - Non-food viewing
Women ill with anorexia nervosa (AN) have been shown to exhibit altered cognitive functioning, particularly poor set-shifting (SS). In this study, we investigated whether brain activation in frontal and parietal regions during visual stimulus processing correlates with SS ability. Women currently ill with AN (AN; N=14), recovered women (REC; N=14) and healthy controls (HC; N=15), viewed alternating blocks of food and non-food pictures during functional magnetic resonance imaging (fMRI). The Berg's Card Sorting Task was completed outside the scanner to measure SS. A priori regions of interest (ROIs) were defined in frontal and parietal regions. The activation during visual stimulus processing in several ROIs correlated positively with poor SS ability in REC, particularly in the left dorsal anterior cingulate cortex (dACC). The correlations with poor SS ability were opposite in AN patients, particularly in the right dACC. These findings underscore that addressing heightened levels of cognitive control associated with higher frontal activation could reduce cognitive inflexibility in recovered women. In AN, greater activation in frontal and parietal regions might be necessary to perform at normal levels during various tasks. Thus, weight restoration could be necessary for AN patients prior to addressing cognitive inflexibility.
Altered food-cue processing in chronically ill and recovered women with anorexia nervosa
Sanders, N. ; Smeets, P.A.M. ; Elburg, A.A. van; Danner, U.N. ; Meer, F. van; Hoek, H.W. ; Adan, R.A.H. - \ 2015
Frontiers in Behavioral Neuroscience 9 (2015). - ISSN 1662-5153 - 12 p.
default mode network - high-calorie foods - eating-disorders - functional-anatomy - reward - fmri - stimuli - leptin - energy - cortex
Anorexia nervosa (AN) is a severe mental disorder characterized by food restriction and weight loss. This study aimed to test the model posed by Brooks et al. (2012a,b) that women suffering from chronic AN show decreased food-cue processing activity in brain regions associated with energy balance and food reward (bottom-up; BU) and increased activity in brain regions associated with cognitive control (top-down; TD) when compared with long-term recovered AN (REC) and healthy controls (HC). Three groups of women, 15 AN (mean illness duration 7.8 ± 4.1 years), 14 REC (mean duration of recovery 4.7 ± 2.7 years) and 15 HC viewed alternating blocks of food and non-food images preceded by a short instruction during functional magnetic resonance imaging (fMRI), after fasting overnight. Functional region of interests (fROIs) were defined in BU (e.g., striatum, hippocampus, amygdala, hypothalamus, and cerebellum), TD (e.g., medial and lateral prefrontal cortex, and anterior cingulate), the insula, and visual processing areas (VPA). Food-cue processing activation was extracted from all fROIs and compared between the groups. In addition, functional connectivity between the fROIs was examined by modular partitioning of the correlation matrix of all fROIs. We could not confirm the hypothesis that BU areas are activated to a lesser extent in AN upon visual processing of food images. Among the BU areas the caudate showed higher activation in both patient groups compared to HC. In accordance with Brooks et al.’s model, we did find evidence for increased TD control in AN and REC. The functional connectivity analysis yielded two clusters in HC and REC, but three clusters in AN. In HC, fROIs across BU, TD, and VPA areas clustered; in AN, one cluster span across BU, TD, and insula; one across BU, TD, and VPA areas; and one was confined to the VPA network. In REC, BU, TD, and VPA or VPA and insula clustered. In conclusion, despite weight recovery, neural processing of food cues is also altered in recovered AN patients.
What you see is what you eat: An ALE meta-analysis of the neural correlates of food viewing in children and adolescents
Meer, F. van; Laan, L.N. van der; Adan, R.A.H. ; Viergever, M.A. ; Smeets, P.A.M. - \ 2015
NeuroImage 104 (2015). - ISSN 1053-8119 - p. 35 - 43.
prader-willi-syndrome - high-calorie foods - orbitofrontal cortex - cognitive control - brain responses - visual-cortex - individual-differences - reward sensitivity - anterior cingulate - obese individuals
Food cues are omnipresent and may enhance overconsumption. In the last two decades the prevalence of childhood obesity has increased dramatically all over the world, largely due to overconsumption. Understanding children's neural responses to food may help to develop better interventions for preventing or reducing overconsumption. We aimed to determine which brain regions are concurrently activated in children/adolescents in response to viewing food pictures, and how these relate to adult findings. Two activation likelihood estimation (ALE) meta-analyses were performed: one with studies in normal weight children/adolescents (aged 8–18, 8 studies, 137 foci) and one with studies in normal weight adults (aged 18–45, 16 studies, 178 foci). A contrast analysis was performed for children/adolescents vs. adults. In children/adolescents, the most concurrent clusters were in the left lateral orbitofrontal cortex (OFC), the bilateral fusiform gyrus, and the right superior parietal lobule. In adults, clusters in similar areas were found. Although the number of studies for a direct statistical comparison between the groups was relatively low, there were indications that children/adolescents may not activate areas important for cognitive control. Overall, the number of studies that contributed to the significant clusters was moderate (6–75%). In summary, the brain areas most consistently activated in children/adolescents by food viewing are part of the appetitive brain network and overlap with those found in adults. However, the age range of the children studied was rather broad. This study offers important recommendations for future research; studies making a direct comparison between adults and children in a sufficiently narrow age range would further elucidate how neural responses to food cues change during development.
Role of the Goat K222-PrPC Polymorphic variant in Prion Infection Resistance
Aguilar-Calvo, P. ; Espinosa, J.C. ; Pintado, B. ; Gutiérrez-Adán, A. ; Alamilo, E. ; Miranda, A. ; Prieto, I. ; Bossers, A. ; Andreoletti, O. ; Torres, J.M. - \ 2014
Journal of Virology 88 (2014)5. - ISSN 0022-538X - p. 2670 - 2676.
bovine spongiform encephalopathy - protein gene polymorphisms - caprine prp gene - natural scrapie - classical scrapie - transgenic mice - sheep - identification - association - genotype
The prion protein-encoding gene (prnp) strongly influences the susceptibility of small ruminants to transmissible spongiform encephalopathies (TSEs). Hence, selective breeding programs have been implemented to increase sheep resistance to scrapie. For goats, epidemiological and experimental studies have provided some association between certain polymorphisms of the cellular prion protein (PrPC) and resistance to TSEs. Among them, the Q/K polymorphism at PrPC codon 222 (Q/K222) yielded the most promising results. In this work, we investigated the individual effects of the K222-PrPC variant on the resistance/susceptibility of goats to TSEs. For that purpose, we generated two transgenic mouse lines, expressing either the Q222 (wild type) or K222 variant of goat PrPC. Both mouse lines were challenged intracerebrally with a panel of TSE isolates. Transgenic mice expressing the wild-type (Q222) allele were fully susceptible to infection with all tested isolates, whereas transgenic mice expressing similar levels of the K222 allele were resistant to all goat scrapie and cattle BSE isolates but not to goat BSE isolates. Finally, heterozygous K/Q222 mice displayed a reduced susceptibility to the tested panel of scrapie isolates. These results demonstrate a highly protective effect of the K222 variant against a broad panel of different prion isolates and further reinforce the argument supporting the use of this variant in breeding programs to control TSEs in goat herds. IMPORTANCE The objective of this study was to determine the role of the K222 variant of the prion protein (PrP) in the susceptibility/resistance of goats to transmissible spongiform encephalopathies (TSEs). Results showed that transgenic mice expressing the goat K222-PrP polymorphic variant are resistant to scrapie and bovine spongiform encephalopathy (BSE) agents. This protective effect was also observed in heterozygous Q/K222 animals. Therefore, the single amino acid exchange from Q to K at codon 222 of the cellular prion protein provides resistance against TSEs. All the results presented here support the view that the K222 polymorphic variant is a good candidate for selective breeding programs to control and eradicate scrapie in goat herds.
Designing the optimal robotic milking barn by applying a queuing network approach
Halachmi, I. ; Adan, I.J.B.F. ; Wald, J. van der; Beek, P. van; Heesterbeek, J.A.P. - \ 2003
Agricultural Systems 76 (2003)2. - ISSN 0308-521X - p. 681 - 696.
dairy-cows - social hierarchy - system - behavior - metabolism - water - potassium - lactation - chlorine - queues
The design of various conventional dairy barns is based on centuries of experience, but there is hardly any experience with robotic milking barns (RMB). Furthermore, as each farmer has his own management practices, the optimal layout is `site dependent¿. A new universally applicable design methodology has been developed, to overcome this lack of experience with RMBs and to facilitate the designing of their optimal layout. This model for optimizing facility allocation, based on cow behaviour, welfare needs, and facility utilization, uses queuing network theory, Markov process, and heuristic optimization. The methodology has been programmed into a software application, supporting the design process. On a particular farm, presented later as a case study, numerical results include: if the herd contains more than 50 cows, the forage-lane utilization is greater than 70% (or idle time is less than 30%). To meet animal-welfare demands, the herd size should not exceed 60 cows. Therefore, the herd should comprise 50¿60 cows. In the second scenario examined, the average robot idle time was 25%, queue length was three cows, and each cow waited for about 3 min at the robot. It is still uncommon to apply techniques from queuing-network theory to livestock housing, and this study demonstrates their potential as practical design tools that meet both economic and animal welfare needs.
Discovery and in vivo evaluation of new melanocortin-4 receptor-selective peptides
Nijenhuis, W.A.J. ; Kruijtzer, J.A.W. ; Wanders, N. ; Vrinten, D.H. ; Garner, K.M. ; Schaaper, W.M.M. ; Meloen, R.H. ; Gispen, W.H. ; Liskamp, R.M. ; Adan, R.A.H. - \ 2003
Peptides 24 (2003)2. - ISSN 0196-9781 - p. 271 - 280.
melanocyte-stimulating hormone - alpha-melanotropin action - agouti-related protein - evaluation in-vitro - biological evaluation - molecular-cloning - inverse agonist - msh analogs - amino-acid - rat
The melanocortin-4 receptor (MC4R) is involved in several physiological processes, including body weight regulation and grooming behaviour in rats. It has also been suggested that the MC4R mediates the effects of melanocortin ligands on neuropathic pain. Selective compounds are needed to study the exact role of the MC4R in these different processes. We describe here the development and evaluation of new melanocortin compounds that are selective for the MC4R as compared with the other centrally expressed receptors, MC3R and MC5R. First, a library of 18 peptides, in which a melanocortin-based sequence was systematically point-mutated, was screened for binding to and activity on the MC3R, MC4R and MC5R. Compound Ac-Nle-Gly-Lys-Image-Phe-Arg-Trp-Gly-NH2 (JK1) appeared to be the most selective MC4R compound, based on affinity. This compound is 90- and 110-fold selective for the MC4R as compared to the MC3R and MC5R, respectively. Subsequent modification of JK1 yielded compound Ac-Nle-Gly-Lys-Image-Nal(2)-Arg-Trp-Gly-NH2 (JK7), a selective MC4R antagonist with 34-fold MC4R/MC3R and 109-fold MC4R/MC5R selectivity. The compounds were active in vivo as determined in a grooming assay and a model for neuropathic pain in rats. Intravenous (i.v.) injections suggested that they were able to pass the blood¿brain barrier. The compounds identified here will be useful in further research on the physiological roles of the MC4R.
The design of robotic dairy barns using closed queuing networks
Halachmi, I. ; Adan, I.J.B.F. ; Wal, J. van der; Heesterbeek, J.A.P. ; Beek, P. van - \ 2000
European Journal of Operational Research 124 (2000)3. - ISSN 0377-2217 - p. 437 - 446.
In this paper we present a closed queueing network model for a robotic milking barn. We use an approximative mean-value algorithm to evaluate important performance criteria such as the number of cows waiting, their waiting time and the utilization of the facilities in the barn. It is shown how the results from the queueing network analysis can support the discussion about the optimal design of the robotic barn.
|Koeienstallen, robots en wachtrijen. Case study
Adan, Y. ; Wal, J. van der; Halachmi, I. ; Beek, P. van - \ 1999
ITW Nieuws 8 (1999)4. - p. 7 - 11.
|Dairy barns and queuing networks
Halachmi, I. ; Adan, I.J.B.F. ; Wal, J. van der; Heesterbeek, J.A.P. ; Beek, P. van - \ 1998
Unknown Publisher - 17 p.
|Synthesis of cyclic alpha-MSH peptides
Schaaper, W.M.M. ; Adan, R.A.H. ; Posthuma, T.A. ; Oosterom, J. ; Gispen, W.H. ; Meloen, R.H. - \ 1998
Letters in peptide science 5 (1998)2-3. - ISSN 0929-5666 - p. 205 - 208.
Cyclic lactam analogs of α-melanocyte stimulating hormone (α-MSH) have been shown to be potent agonists in the frog skin bioassay [Al-Obeidi, F. et al., J. Med. Chem., 32 (1989) 2555], demonstrating melanocortin-1 (MC1) receptor activity. We synthesized cyclic α-MSH(1-13) and α-MSH(4-10) lactam analogs. The peptides were synthesized using Fmoc chemistry. We improved the cyclization procedure: side chains of Asp5 and Lys10 from the deprotected peptide were coupled in DMF to form a cyclic lactam, using an excess of PyBOP reagent and DIEA as a base. The cyclization reaction was completed within 1 h and was almost quantitative. We also synthesized an α-MSH analog cyclized via a disulphide bridge. The peptides were tested for their selectivity for the rat MC4 receptor. Cyclization and substitutions at position 7 dramatically influenced the selectivity for the rMC4 receptor.
|Neurite outgrowth in Neuro 2A cells is stimulated by activation of melanocortin receptors.
Adan, R.A.H. ; Kraan, M. van de; Oosterom, J. ; Wiegant, V.M. ; Burbach, J.P.H. ; Gispen, W.H. - \ 1995
In: Proc. 25th Annual Meeting Society for Neuroscience. San Diego (1995) 228.7
|Differential effects of melanocortin peptides on neural melanocortin receptors.
Adan, R.A.H. ; Oosterom, J. ; Wiegant, V.M. ; Burbach, J.P.H. ; Gispen, W.H. - \ 1995
In: Proc. 24th Annual meeting Society for Neuroscience. Miami Beach (1995) 220.4