Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers

Permeability coefficients across monolayers of the human colon carcinoma cell line Caco-2, cultured on permeable supports, are commonly used to predict the absorption of orally administered drugs and other xenobiotics. This protocol describes our method for the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model. A few modifications that have been introduced over the years are incorporated in the protocol. The method can be used to trace the permeability of a test compound in two directions, from the apical to the basolateral side or vice versa, and both passive and active transport processes can be studied. The permeability assay can be completed within one working day, provided that the Caco-2 monolayers have been cultured and differentiated on the permeable supports 3 weeks in advance.     

Gender-specific links between hepatic 11beta reduction of cortisone and adipokines

Objective: Reduction of cortisone to cortisol is mediated by 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1), a putative key enzyme in obesity‐related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor‐α (TNF‐α), are of importance for 11βHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender‐specific and associated with circulating levels of leptin and TNF‐α receptors and/or sex hormones. Research Methods and Procedures: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11βHSD1 enzyme activity was estimated by the conversion of orally‐ingested cortisone to cortisol. Results: Hepatic 11βHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF‐α receptors also after adjustment of BMI and waist circumference. In contrast, 11β reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. Discussion: Hepatic 11β reduction shows different links to circulating adipocyte‐derived hormones in males and females. This emphasizes the need for further studies on tissue‐specific regulation of 11βHSD1 in both genders.     

Surfing on the seascape: Adaptation in a changing environment

The environment changes constantly at various time scales and, in order to survive, species need to keep adapting. Whether these species succeed in avoiding extinction is a major evolutionary question. Using a multilocus evolutionary model of a mutation‐limited population adapting under strong selection, we investigate the effects of the frequency of environmental fluctuations on adaptation. Our results rely on an “adaptive‐walk” approximation and use mathematical methods from evolutionary computation theory to investigate the interplay between fluctuation frequency, the similarity of environments, and the number of loci contributing to adaptation. First, we assume a linear additive fitness function, but later generalize our results to include several types of epistasis. We show that frequent environmental changes prevent populations from reaching a fitness peak, but they may also prevent the large fitness loss that occurs after a single environmental change. Thus, the population can survive, although not thrive, in a wide range of conditions. Furthermore, we show that in a frequently changing environment, the similarity of threats that a population faces affects the level of adaptation that it is able to achieve. We check and supplement our analytical results with simulations.     

Expression of inflammatory cytokines in mesenchymal stromal cells is sensitive to culture conditions and simple cell manipulations

Background

Mesenchymal stromal cells (MSCs) can be used in several clinical applications. While MSCs are frequently cultured in fetal bovine serum for in vitro experimentation, human serum supplements are required for cells to be used in patients. Here we show how different human serum supplements and in vitro manipulations used during the cell culture impact on MSC proliferation rate and expression of inflammatory molecules.

Fish larvae distribution among different habitats in coastal East Africa

Fish larvae abundances, diversity and trophic position across shallow seagrass, coral reef and open water habitats were examined to characterize their distribution in coastal East Africa. Larvae were identified to family and analysed for abundance differences between sites and habitats, trophic level using stable-isotope analysis and parental spawning mode. Abundances differed greatly between sites with the highest numbers of larvae occurring in the open-water and seagrass habitats. Larval fish diversity was high across habitats with 51 families identified with small differences between sites and among habitats. Notably, larvae of abundant large herbivorous fishes present in reef and seagrass habitats were almost completely absent at all sampling locations. In the seagrass, demersal spawned larvae were more abundant compared with the reef and open-water habitats. Stable-isotope analysis revealed that fish larvae have a varied diet, occupying trophic level two to three and utilizing planktonic prey. This study offers new insights into distributional aspects of fish larvae along the East African coast where such information is sparse.     

Wood addition in the hatchery and river environments affects post‐release performance of overwintering brown trout

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The first specimen of Archaeopteryx from the Upper Jurassic Mörnsheim Formation of Germany

From an initial isolated position as the oldest evolutionary prototype of a bird, Archaeopteryx has, as a result of recent fossil discoveries, become embedded in a rich phylogenetic context of both more and less crownward stem-group birds. This has prompted debate over whether Archaeopteryx is simply a convergently bird-like non-avialan theropod. Here we show, using the first synchrotron microtomographic examination of the genus, that the eighth or Daiting specimen of Archaeopteryx possesses a character suite that robustly constrains it as a basal avialan (primitive bird). The specimen, which comes from the Mörnsheim Formation and is thus younger than the other specimens from the underlying Solnhofen Formation, is distinctive enough to merit designation as a new species, Archaeopteryx albersdoerferi sp. nov., but is recovered in close phylogenetic proximity to Archaeopteryx lithographica. Skeletal innovations of the Daiting specimen, such as fusion and pneumatization of the cranial bones, well vascularized pectoral girdle and wing elements, and a reinforced configuration of carpals and metacarpals, suggest that it may have had more characters seen in flying birds than the older Archaeopteryx lithographica. These innovations appear to be convergent on those of more crownward avialans, suggesting that Bavarian archaeopterygids independently acquired increasingly bird-like traits over time. Such mosaic evolution and iterative exploration of adaptive space may be typical for major functional transitions like the origin of flight.     

Inter‐individual variation in colour patterns in noctuid moths characterizes long‐distance dispersers and agricultural pests

A high capacity for long‐distance dispersal is a key to success for species confronted with environmental heterogeneity, habitat modification, fragmentation and loss. However, dispersal capacity is difficult to quantify and therefore poorly known in most taxa. Here, we report on a test for an association of variation in dispersal capacity with variable colouration of noctuid moths. First, using data from 12 experienced lepidopterologists, we showed that despite variation among experts in average assessments, different species are consistently classified as having non‐variable, variable or highly variable colour patterns when assessed by different experts. We then compared the incidence of non‐resident species with high inter‐individual variation in colour patterns recorded on the isolated island Utklippan (n = 47), with that in a species pool of potential long‐distance dispersers from the nearest mainland (n = 295). Species with high inter‐individual colour pattern variation were over‐represented on the island compared with species having non‐variable colouration. This finding constitutes rare evidence from the wild of long‐distance dispersal, measured on a spatial scale relevant for moths when tracking habitats in fragmented and changing landscapes or when keeping pace with environmental challenges associated with climate change. Finally, we showed that Swedish noctuid moths classified as agricultural pests (n = 28) had more variable colour patterns compared with non‐pests (n = 368). The majority of agricultural pests were also recorded on the isolated island, an outcome that is indicative of pest species having high dispersal capacity. Data on colour pattern variation may thus offer a simple and cost‐effective proxy to estimate dispersal capacity and can also help identify potential pest species. Our findings are potentially useful when modelling and predicting population and range dynamics of species in spatiotemporally heterogeneous environments, with direct implications for conservation biology and pest management.