Identification of enterodiol as a masker for caffeine bitterness by using a pharmacophore model based on structural analogues of homoeriodictyol

Starting from previous structure-activity relationship studies of taste modifiers based on homoeriodictyol, dihydrochalcones, deoxybenzoins, and trans-3-hydroxyflavones as obvious analogues were investigated for their masking effect against caffeine. The most active compounds of the newly investigated taste modifiers were phloretin, the related dihydrochalcones 3-methoxy-2',4,4'-trihydroxydihydrochalcone and 2',4-dihydroxy-3-methoxydihydrochalcone, and the deoxybenzoin 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)ethanone. Starting with the whole set of compounds showing activity >22%, a (Q)SAR pharmacophore model for maskers of caffeine bitterness was calculated to explain the structural requirements. After docking of the pharmacophore into a structural model of the broadly tuned bitter receptor hTAS2R10 and docking of enterolactone and enterodiol as only very weakly related structures, it was possible to predict qualitatively their modulating activity. Enterodiol (25 mg L(-1)) reduced the bitterness of the 500 mg L(-1) caffeine solution by about 30%, whereas enterolactone showed no masking but a slight bitter-enhancing effect.     

Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.     

Flash chromatography on cartridges for the separation of plant extracts: Rules for the selection of chromatographic conditions and comparison with medium pressure liquid chromatography

Empirical rules for the selection of chromatographic conditions on flash chromatography cartridges were developed, with an emphasis on gradient mode. These rules were then tested with separation of extracts from important medicinal plants including Curcuma xanthorrhiza, Piper nigrum and Salvia milthiorrhiza. Sepacore® cartridges enabled a good separation of compounds with a broad range of polarity, as typically found in plant extracts. The chromatographic resolution remained, however, lower than that achieved on classical columns packed with material of smaller particle size. For poorly soluble extracts, solid introduction gave better results than liquid injection.     

Aesthetic preferences of non-farmers and farmers for different land-use types and proportions of ecological compensation areas in the Swiss lowlands

Beyond its traditional function of food production, agricultural land offers public amenities such as the protection of natural resources and landscape scenery. This study investigates the preferences of non-farmers and farmers for nine landscape scenarios in the Swiss lowlands. The nine landscapes were the result of a photo editing process combining three land-use types (arable crops, grassland and a mixture of both) and three proportions of ecological compensation areas (0%, 10% and 30%). The landscape photographs were randomly arranged on one page of a paper-based questionnaire which was sent to a random sample of 4000 Swiss households (non-farmers) and 500 farmers. The respondents (1376 non-farmers and 276 farmers) rated each landscape by attractiveness. Both non-farmers and farmers preferred a mixed land-use type or one dominated by arable crops over one dominated by grassland. Non-farmers’ preference ratings were highly influenced by the proportion of ecological compensation areas (ECAs) in the rated landscape: Non-farmers rated a landscape with a mixed land-use type and 30% ECAs highest, whereas farmers rated a landscape dominated by arable crops and 10% ECAs highest. The results indicate that heterogeneous landscapes (mixed land use, high proportion of ECAs) influence scenic beauty positively. Thus, farming practices and agro-environment schemes such as ECAs can have an impact on the visual attractiveness of a landscape.     

Ceramide triggers budding of exosome vesicles into multivesicular endosomes

Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal membrane and that the transfer of exosome-associated domains into the lumen of the endosome did not depend on the function of the ESCRT (endosomal sorting complex required for transport) machinery, but required the sphingolipid ceramide. Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation.