Alcohol representations are socially situated: an investigation of beverage representations by using a property generation task

Previous research suggests that people's representations of alcoholic beverages play an important role in drinking behavior. However, relatively little is known about the contents of these representations. Here, we introduce the property generation task as a tool to explore these representations in detail. In a laboratory study (N = 110), and a bar field-study (N = 56), participants listed typical properties of alcoholic beverages, sugary beverages, and water. Each of these properties was then categorized using a previously developed, hierarchical coding scheme. For example, the property “sweet” was categorized as referring to “taste”, which falls under “sensory experience”, which falls under “consumption situation”. Afterwards, participants completed measures of drinking behavior and alcohol craving. Results showed that alcoholic beverages were strongly represented in terms of consumption situations, with 57% and 69% of properties relating to consumption in the laboratory and the bar study, respectively. Specifically, alcoholic beverages were more strongly represented in terms of the social context of consumption (e.g., “with friends”) than the other beverages. In addition, alcoholic beverages were strongly represented in terms of sensory experiences (e.g. “sweet”) and positive outcomes (e.g. “creates fun”), as were the sugary beverages and water. In Study 1, the extent to which alcoholic beverages were represented in terms of social context was positively associated with craving and regularly consuming alcohol. The property generation task provides a useful tool to access people's idiosyncratic representations of alcoholic beverages. This may further our understanding of drinking behavior, and help to tailor research and interventions to reduce drinking of alcoholic and other high-calorie beverages

Physics-based generative model of curvature sensing peptides; distinguishing sensors from binders

Proteins can specifically bind to curved membranes through curvature-induced hydrophobic lipid packing defects. The chemical diversity among such curvature “sensors” challenges our understanding of how they differ from general membrane “binders” that bind without curvature selectivity. Here, we combine an evolutionary algorithm with coarse-grained molecular dynamics simulations (Evo-MD) to resolve the peptide sequences that optimally recognize the curvature of lipid membranes. We subsequently demonstrate how a synergy between Evo-MD and a neural network (NN) can enhance the identification and discovery of curvature sensing peptides and proteins. To this aim, we benchmark a physics-trained NN model against experimental data and show that we can correctly identify known sensors and binders. We illustrate that sensing and binding are phenomena that lie on the same thermodynamic continuum, with only subtle but explainable differences in membrane binding free energy, consistent with the serendipitous discovery of sensors

Improved bioaccessibility of polymethoxyflavones loaded into high internal phase emulsions stabilized by biopolymeric complexes : a dynamic digestion study via TNO's gastrointestinal model

In this work, the bioaccessibility of polymethoxyflavones (PMFs) loaded in high internal phase emulsions (HIPE, ϕoil = 0.82) stabilized by whey protein isolate (WPI)-low methoxy pectin (LMP) complexes was evaluated using in vitro lipolysis and dynamic in vitro intestinal digestion studies. PMFs loaded HIPE was prepared by using aqueous dispersion of pre-formed biopolymeric complexes (WPI-LMP, 2:1 ratio) as the external phase and medium chain triglycerides oil (containing PMFs extracted from citrus peel) as the dispersed phase. The in vitro lipolysis study revealed that PMFs in HIPE became bioaccessible much higher than PMFs in medium chain triacylglycerols oil (MCT oil). In addition, by simulating the entire human gastrointestinal (GI) tract, the GI model TIM-1 demonstrated a 5- and 2-fold increase in the total bioaccessibility for two major PMFs encapsulated in HIPE, i.e. tangeretin (TAN) and nobiletin (NOB), respectively, as opposed to PMFs in MCT oil. Together these results from the digestion study showed that the incorporation of a high amount of PMFs into the viscoelastic matrix of HIPE could represent an innovative and effective way to design an oral delivery system. Such a system could be used to control and to improve the delivery of lipophilic bioactive compounds within the different compartments of the digestive tract, especially the human upper GI tract

Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach

Developmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication. The fields of DNT/RT would greatly benefit from in vitro tests that allow the identification of toxicant-induced changes of the cellular proteostasis, or of its underlying transcriptome network. Therefore, the 'human embryonic stem cell (hESC)- derived novel alternative test systems (ESNATS)' European commission research project established RT tests based on defined differentiation protocols of hESC and their progeny. Valproic acid (VPA) and methylmercury (MeHg) were used as positive control compounds to address the following fundamental questions: (1) Does transcriptome analysis allow discrimination of the two compounds? (2) How does analysis of enriched transcription factor binding sites (TFBS) and of individual probe sets (PS) distinguish between test systems? (3) Can batch effects be controlled? (4) How many DNA microarrays are needed? (5) Is the highest non-cytotoxic concentration optimal and relevant for the study of transcriptome changes? VPA triggered vast transcriptional changes, whereas MeHg altered fewer transcripts. To attenuate batch effects, analysis has been focused on the 500 PS with highest variability. The test systems differed significantly in their responses (\20 % overlap). Moreover, within one test system, little overlap between the PS changed by the two compounds has been observed. However, using TFBS enrichment, a relatively large 'common response' to VPA and MeHg could be distinguished from 'compound-specific' responses. In conclusion, the ESNATS assay battery allows classification of human DNT/RT toxicants on the basis of their transcriptome profiles.EU/FP7/ESNATSDFGDoerenkamp-Zbinden Foundatio

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Bioavailability of folate from fortified milk products

The gap between actual intake and recommended intake of folate could be bridged by the consumption of fortified food products. Milk is considered as a potential food matrix for folate fortification in countries (such as theNetherlands) witha highmilk consumption. The aim of the work described in this thesis was to study the bioavailability of folate from milk products to establish whether milk is a suitable matrix for fortification with folic acid or 5-CH 3 -H 4 folate. In addition, the role of folate-binding proteins (FBP) in the bioavailability of folate from milk was investigated.Studies with a dynamic in vitro gastrointestinal model showed that folic acid and 5-CH 3 -H 4 -folate are highly bioaccessible from fortified milk products. The bioaccessibility of folate from fortified milk products was lower in presence of additional FBP, with a more pronounced inhibitory effect for folic acid as compared with 5-CH 3 -H 4 folate. This was explained by the observed difference in extent of binding to FBP between folic acid and 5-CH 3 -H 4 -folate in the duodenal lumen. Before gastric passage, folic acid and 5-CH 3 -H 4 -folate were mainly bound to FBP (76-79%) while 7% was free. After gastric passage, folic acid remained bound to FBP to a similar extent (80-81%). For 5-CH 3 -H 4 -folate the FBP-bound fraction gradually decreased from 79% to 5% and the free fraction increased from 7% to 93%. So, while folic acid enters the proximal part of the small intestine bound to FBP, 5-CH 3 -H 4 -folate appears mainly to be present as free folate in the duodenal lumen. The intestinal absorption of folic acid and 5-CH 3 -H 4 folate was studied using monolayers of human colon carcinoma (Caco-2) cells. Only a small difference in transport, in rate and underlying transport mechanisms, across Caco-2 cells was found between folic acid and 5-CH 3 -H 4 -folate. In presence of FBP, the absorption of folic acid and 5-CH 3 -H 4 folate was found to be lower and dependent on the extent of binding to FBP at the luminal side of the intestinal cells.Results from a human intervention study showed that the consumption of 200mg of folic acid added to milk significantly increased folate concentrations in serum and red blood cells. Although only two fortified milk products were tested in a human study, several milk products fortified with folic acid or 5-CH 3 -H 4 -folate with or without additional FBP were tested in the in vitro studies with the gastrointestinal model. Finally, a kinetic model was used to integrate the in vitro results about the kinetics of folate bioaccessibility and intestinal absorption and to extrapolate the findings to the human situation. With this in silico approach, the blood folate levels in humans could be predicted accurately.In conclusion, the in vitro and in vivo studies described in this thesis show that milk is an appropriate food matrix for folate fortification. A dietary strategy with fortified milk products can be recommended to bridge the gap between actual and recommended folate intake to optimize the folate status of the population. Folic acid-fortified milk should, however, not be supplemented with additional FBP as this will lead to a lower bioavailability of folic acid