Suchergebnisse

Transboundary haze pollution as a result of indiscriminate land clearance by fire has significant health and economic impacts on member states of the Association of South-east Asian Nations (ASEAN). Meanwhile the impact of the associated carbon emissions, ecological disturbance and biodiversity loss extends well beyond South-east Asia. This is despite the fact there are relatively well-established mechanisms to combat forest fires, and policy-level solutions have existed on paper for years. Although the fires are mostly in Indonesian territory, the involvement of multiple hierarchies of stakeholders in Indonesia, Malaysia and Singapore adds complexity to the quest for lasting solutions. A more robust approach is required from the region's governments, especially in instilling accountability among large companies, and this is feasible without increasing political tensions within ASEAN. Indonesia's ratification of the Haze Agreement is a significant development but needs to be complemented with actions at the local (e.g. grassroot initiatives in forest protection, firefighting, policing of illegal clearance practices), national (e.g. centralizing ministry-level control of forestry resources) and regional levels (e.g. implementing compliance mechanisms and legal standards to tackle haze and forest fires). Ultimately, actions to combat forest fires may also help secure the long-term conservation of biodiversity-rich peat swamps. Rather than being a source of discord, combating haze pollution could become South-east Asia's defining environmental project.

Transboundary haze pollution as a result of indiscriminate land clearance by fire has significant health and economic impacts on member states of the Association of South-east Asian Nations (ASEAN). Meanwhile the impact of the associated carbon emissions, ecological disturbance and biodiversity loss extends well beyond South-east Asia. This is despite the fact there are relatively well-established mechanisms to combat forest fires, and policy-level solutions have existed on paper for years. Although the fires are mostly in Indonesian territory, the involvement of multiple hierarchies of stakeholders in Indonesia, Malaysia and Singapore adds complexity to the quest for lasting solutions. A more robust approach is required from the region's governments, especially in instilling accountability among large companies, and this is feasible without increasing political tensions within ASEAN. Indonesia's ratification of the Haze Agreement is a significant development but needs to be complemented with actions at the local (e.g. grassroot initiatives in forest protection, firefighting, policing of illegal clearance practices), national (e.g. centralizing ministry-level control of forestry resources) and regional levels (e.g. implementing compliance mechanisms and legal standards to tackle haze and forest fires). Ultimately, actions to combat forest fires may also help secure the long-term conservation of biodiversity-rich peat swamps. Rather than being a source of discord, combating haze pollution could become South-east Asia's defining environmental project.

The Fukushima disaster was a wake-up call for the nuclear industry as well as a shocking revelation of the inner workings of the Japanese power sector. The political fallout from the event was far-reaching, pushing governments into abandoning nuclear expansion, turning instead to fossil fuels and renewable energy alternatives. While the move away from nuclear energy was deemed a move critical to political survival in Europe, we find that political candidates running on anti-nuclear platforms did not win elections, while the pro-nuclear Liberal Democratic Party won government in the 2012 elections. Against this backdrop, we analyse the energy conflict in Japan using a framework of values versus interests and consider the regulatory and cultural conditions that contributed to the disaster. A number of considerations lie in the way of an organised phase-out of nuclear power in Japan. We also consider the possible policy paths Japan may take.

The Fukushima disaster was a wake-up call for the nuclear industry as well as a shocking revelation of the inner workings of the Japanese power sector. The political fallout from the event was far-reaching, pushing governments into abandoning nuclear expansion, turning instead to fossil fuels and renewable energy alternatives. While the move away from nuclear energy was deemed a move critical to political survival in Europe, we find that political candidates running on anti-nuclear platforms did not win elections, while the pro-nuclear Liberal Democratic Party won government in the 2012 elections. Against this backdrop, we analyse the energy conflict in Japan using a framework of values versus interests and consider the regulatory and cultural conditions that contributed to the disaster. A number of considerations lie in the way of an organised phase-out of nuclear power in Japan. We also consider the possible policy paths Japan may take.

Yong-Hui Ding,1,2 Zhi-Wei Zhou,2,3 Chun-Fang Ha,1 Xue-Yu Zhang,1 Shu-Ting Pan,4 Zhi-Xu He,3 Jeffrey L Edelman,2 Dong Wang,5 Yin-Xue Yang,6 Xueji Zhang,7 Wei Duan,8 Tianxin Yang,9 Jia-Xuan Qiu,4 Shu-Feng Zhou2,3 1Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA ; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 5Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 6Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People's Republic of China; 8School of Medicine, Deakin University, Waurn Ponds, Australia; 9Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA Abstract: Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5′-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer. Keywords: alisertib, Aurora kinase A, epithelial ovarian cancer, cell cycle, apoptosis, autophagy, epithelial to mesenchymal transition, sirtuin 1