Transmigration characteristics of breast cancer and melanoma cells through the brain endothelium: Role of Rac and PI3K

Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer.     

Bioluminescence‐based assays for assessing eco‐ and genotoxicity of airborne emissions

Ecotoxicological tests (or bioassays) are controlled, reproducible tests where ecological responses are determined quantitatively. Due to numerous difficulties arising when airborne emissions are sampled, relatively few ecotoxicological assays have been applied. Aerosol particles are generally collected on a filter, which limits the quantity of the sample, thus also limiting the range of available test organisms. Bacterial bioassays require low sample quantity, and make a good choice when eco‐ or genotoxicity of the sample are to be determined. Of bacterial assays, the bioluminescence inhibition test has been proven applicable for assessing toxicity of airborne contaminants. In this paper diverse test protocols and their modifications are reviewed. Copyright © 2016 John Wiley & Sons, Ltd.     

Chiral Separation of Uncharged Pomalidomide Enantiomers Using Carboxymethyl‐β‐Cyclodextrin: A Validated Capillary Electrophoretic Method

The racemic mixture of pomalidomide (POM), a second‐generation immunomodulatory uncharged drug, was separated into enantiomers by capillary zone electrophoresis for the first time. Seven different chargeable cyclodextrin (CD) derivatives were screened as complexing agents and chiral selectors, investigating the stability of the POM‐CD inclusion complexes and their enantiodiscriminating capacities. Based on preliminary experiments, carboxymethyl‐β‐CD (CM‐β‐CD) was found to be the most effective chiral selector. Factors influencing enantioseparation were systematically optimized, using an orthogonal experimental design. Optimal parameters (background electrolyte [BGE]: 50 mM Tris‐acetate buffer, pH 6.5, containing 15 mM CM‐β‐CD; capillary temperature: 20°C; voltage applied +15 kV) allowed baseline separation of POM enantiomers with a resolution as high as 4.87. The developed method was validated, in terms of sensitivity (limit of detection and limit of quantification), linearity, accuracy, repeatability, and intermediate precision. Chirality 28:199–203, 2016. © 2015 Wiley Periodicals, Inc.     

Home ranges in moving habitats: polar bears and sea ice

Home range size estimates are often used to assess the amount of space required for animals to perform the activities essential for their survival and reproduction. However, in moving environments, traditional home range estimates may be ill suited to this task. In particular, traditional home range estimates are inaccurate representations of the space required by polar bears Ursus maritimus. The sea ice is the prime foraging platform of polar bears, and estimating the amount of ice encountered by bears may provide a better approximation of space use. We develop a technique to make these estimates. Our results confirm that polar bears use more space than terrestrial carnivores to find the resources and conditions they require. We also show that the traditional geographic home range can underestimate both the movement of bears and the amount of space encountered. Moreover, area of ice encountered increased with ice drift, indicating that bears living on highly mobile ice might be exposed to higher energetic costs, and potentially larger energetic gains, than bears inhabiting more stable ice. The methods and concepts presented here can serve as a foundation for new approaches to study the space use of the many species living in moving environments.     

Large‐brained birds suffer less oxidative damage

Large brains (relative to body size) might confer fitness benefits to animals. Although the putative costs of well‐developed brains can constrain the majority of species to modest brain sizes, these costs are still poorly understood. Given that the neural tissue is energetically expensive and demands antioxidants, one potential cost of developing and maintaining large brains is increased oxidative stress (‘oxidation exposure’ hypothesis). Alternatively, because large‐brained species exhibit slow‐paced life histories, they are expected to invest more into self‐maintenance such as an efficacious antioxidative defence machinery (‘oxidation avoidance’ hypothesis). We predict decreased antioxidant levels and/or increased oxidative damage in large‐brained species in case of oxidation exposure, and the contrary in case of oxidation avoidance. We address these contrasting hypotheses for the first time by means of a phylogenetic comparative approach based on an unprecedented data set of four redox state markers from 85 European bird species. Large‐brained birds suffered less oxidative damage to lipids (measured as malondialdehyde levels) and exhibited higher total nonenzymatic antioxidant capacity than small‐brained birds, whereas uric acid and glutathione levels were independent of brain size. These results were not altered by potentially confounding variables and did not depend on how relative brain size was quantified. Our findings partially support the ‘oxidation avoidance’ hypothesis and provide a physiological explanation for the linkage of large brains with slow‐paced life histories: reduced oxidative stress of large‐brained birds can secure brain functionality and healthy life span, which are integral to their lifetime fitness and slow‐paced life history.     

Transcriptional Heterogeneity of Beta Cells in the Intact Pancreas

1. Download high-res image (385KB)
2. Download full-size image

     

Worldwide distribution and theoretical spreading of Trichoferus campestris (Coleoptera: Cerambycidae) depending on the main climatic elements

The velvet longhorned beetle, Trichoferus campestris (Coleoptera: Cerambycidae) is a serious wood‐boring pest that is a major threat to the phytosanitary condition of forests and orchards. Its worldwide expansion is a major concern for plant health. We have collected all bibliographical references, phytosanitary reports and authentic photographic evidence from entomological websites to determine the worldwide distribution of T. campestris. The theoretical directions of the spreading and actually occupied area of this arthropod pest were determined over the whole Holarctic range. Furthermore, the potential distribution area was calculated using cumulated temperature in the growing season averaged over 15 years both in the Palearctic and Nearctic regions. Holarctic expansion of the species, including the main parts of North America and Eurasia, is clearly indicated. Its populations occur in 29 countries to date, supported by documentation from 64 publications and 30 online forums. Its spread is continuously westward in the Palearctic; in the Nearctic, the spread was first southward from the Great Lakes region then eastward from Utah. The species has excellently adapted to circumstances of freight by ship and plane, as wood is often used, ensuring optimal conditions for the pest. In addition, the active spreading achieved by flying is an important factor contributing to its expansion. The primary criterion for controlling the species would be the introduction of a monitoring system in affected and exposed areas.     

Divergent microsatellite evolution in the human and chimpanzee lineages

Comparison of the complete human genome sequence to one of its closest relatives, the chimpanzee genome, provides a unique opportunity for exploring recent evolutionary events affecting the microsatellites in these species. A simple assumption on microsatellite distribution is that the total length of perfect repeats is constant compared to that of imperfect ones regardless of the repeat sequence. In this paper, we show that this is valid for most of the chimpanzee genome but not for a number of human chromosomes. Our results suggest accelerated evolution of microsatellites in the human genome relative to the chimpanzee lineage.