Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice

Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors.We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in the skin tissue extract. Absence of cystatin C in these transgenic mice resulted in more progression of dysplasia to carcinoma in situ on the face, ear, chest, and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse serum sample ELISA, tissue immunohistological analysis, and tissue extract-mediated in vitro elastinolysis and collagenolysis assays demonstrated that cystatin C deficiency significantly increased cathepsin expression and activity. In skin from both the chest and ear, we found that the absence of cystatin C reduced epithelial cell apoptosis but increased proliferation. From the same tissue preparations, we detected significantly higher levels of pro-angiogenic laminin 5-derived γ2 peptides and concurrently increased neovascularization in cystatin C-deficient mice, compared to those from wild-type control mice.Enhanced cathepsin expression and activity in cystatin C-deficient mice contributed to the progression of dysplasia by altering premalignant tissue epithelial proliferation, apoptosis, and neovascularization

Consumption-based accounting of CO2 emissions in the sustainable development Goals Agenda

In 2017 the paper “The Sustainable Development Oxymoron: Quantifying and Modelling the Incompatibility of Sustainable Development Goals" (Spaiser et al. 2017) was published, showing that there is a conflict between socio-economic development goals and ecological sustainability goals using cross-country time-series data. The authors looked at production-based CO2 emissions to measure and model the 13th SDG goal addressing climate change. Their models showed that production-based CO2 emissions were stalling or even decreasing in rich countries, which suggests that other countries are also likely to see stalling and decrease in their CO2 emissions once they become rich. However, this conclusion can be challenged when accounting for consumption-based CO2 emissions rather than production-based CO2 emissions. In this follow-up paper, we re-run some of the analyses performed in the original paper making use of consumption-based CO2 emissions. The analysis confirms the inherent SDG conflict between socio-economic and ecological SDGs. But, this new analysis demonstrates that from a consumption perspective the trend of stalling or decreasing CO2 emissions is reversed, with natural depletion costs being exported to poorer countries. Despite this new perspective on CO2 emissions, the conflict between SDG goals can still be avoided by making investments in public health, education and renewable energy, as suggested in the original paper