Yili Zhou

Background: Endothelins are paracrine peptides with growth-promoting and vasoactive functions for a variety of cell types. Elevated activation of the endothelin signaling pathway induces cell proliferation and/or survival and is implicated in a variety of malignancies. Increased endothelin 1 was described in solar lentigines in previous reports, raising the possibility that the endothelin pathway may be of significance in keratinocyte proliferation-related disorders. However, detailed investigation on endothelins in skin malignancies is lacking. Objectives: This study aims to survey the expression of endothelins and their receptors in keratinocyte-derived benign and malignant tumors of the skin and to test the effects of endothelin inhibitors on the growth and survival of cultured keratinocytes. Methods: Quantitative polymerase chain reaction was used to measure the level of gene transcription of three endothelins and two endothelin receptors. The genes with significant messenger ribonucleic acid expression abnormalities were confirmed with immunohistochemical analysis to examine expression differences at the protein levels. To analyze the effect of endothelin inhibitors on the keratinocyte growth and survival, keratinocytes were cultured in the presence of various concentrations of endothelin inhibitors and subjected to tetrazolium bromide assay to quantify the cell numbers over time. Results: ET-1 mRNA was found to be significantly up-regulated in seborrheic keratosis and basal cell carcinoma. However, no significant expression increase was found in actinic keratosis, Bowen's disease, or squamous cell carcinoma. Immunohistochemical analysis of ET-1 peptide confirmed increased expression. In cultured keratinocytes, peptide inhibitors of the endothelin pathway resulted in a marked reduction in cell survival. Conclusion: The endothelin signaling pathway, especially ET-1, is activated in basoloid keratinocyte neoplasms of the skin, such as basal cell carcinoma and seborrheic keratosis. Blockade of this pathway can reduce cell survival in vitro. Therefore, endothelin inhibitors potentially offer a novel method for the treatment of some keratinocyte-derived skin tumors.

© 2014 Li et al. Aedes albopictus is a very invasive and aggressive insect vector that causes outbreaks of dengue fever, chikungunya disease, and yellow fever in many countries. Vector ecology and disease epidemiology are strongly affected by environmental changes. Urbanization is a worldwide trend and is one of the most ecologically modifying phenomena. The purpose of this study is to determine how environmental changes due to urbanization affect the ecology of Aedes albopictus. Aquatic habitats and Aedes albopictus larval population surveys were conducted from May to November 2013 in three areas representing rural, suburban, and urban settings in Guangzhou, China. Ae. albopictus adults were collected monthly using BG-Sentinel traps. Ae. albopictus larva and adult life-table experiments were conducted with 20 replicates in each of the three study areas. The urban area had the highest and the rural area had the lowest number of aquatic habitats that tested positive for Ae. albopictus larvae. Densities in the larval stages varied among the areas, but the urban area had almost two-fold higher densities in pupae and three-fold higher in adult populations compared with the suburban and rural areas. Larvae developed faster and the adult emergence rate was higher in the urban area than in suburban and rural areas. The survival time of adult mosquitoes was also longer in the urban area than it was in suburban and rural areas. Study regions, surface area, water depth, water clearance, surface type, and canopy coverage were important factors associated with the presence of Ae. albopictus larvae. Urbanization substantially increased the density, larval development rate, and adult survival time of Ae. albopictus, which in turn potentially increased the vector capacity, and therefore, disease transmissibility. Mosquito ecology and its correlation with dengue virus transmission should be compared in different environmental settings.

Many moral error theorists reject moral realism on the grounds that moral realism implies the existence of categorical normativity, yet categorical normativity does not exist. Call this the Metaphysical Argument. In response, some moral realists have emphasized a parity between moral normativity and epistemic normativity. They argue that if one kind of normativity is rejected, then both must be rejected. Therefore, one cannot be a moral error theorist without also being an epistemic error theorist. Call this the Parity Argument. In this paper, we address three possible responses to the Parity Argument from moral error theorists: (1) accept the parity but still reject epistemic error theory, (2) reject the parity, (3) accept the parity and defend epistemic error theory. We argue that there are problems with each of these responses, so the Parity Argument stands as a strong counterargument to the Metaphysical Argument. We conclude by drawing some lessons for any future challenges to the Parity Argument.