Ca2+ monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor

Calcium (Ca2+)-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (300?nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca2+ level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca2+ signaling in P. falciparum and is applicable for drug screening.We are grateful to Japanese Red Cross Blood Society for providing human RBC and plasma. We also thank Tanaka R, Ogoshi (Sakura) M and Matsumoto N for technical assistance and Templeton TJ for critical reading. This study was conducted at the Joint Usage / Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan. KP was a Tokyo Biochemical Research Foundation (TBRF, http://www.tokyobrf.or.jp) post-doctoral fellow and PEF was a Japanese Society of Promotion Sciences (JSPS) post-doctoral fellow. This work was supported in part by the TBRF (K.P.), JSPS (P.E.F.), Takeda Science Foundation (K.Y.), Grants-in-Aids for Scientific Research 24590509 (K.Y.), 22390079 (O.K.), and for Scientific Research on Innovative Areas 23117008 (O.K.), MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Political Transitions and Macro-level Foundations of Political Stability

Why do some political transitions end peacefully while others give rise to instability and conflict? Starting from the\u2018Third Wave\u2019of democratization in the Seventies, an optimist outlook has traditionally accompanied the demise of authoritarian regimes, and the idea of\u2018exporting democracy\u2019possibly represents the peak of such position. Yet, conflicts that ensued the end of the Communist bloc, failed transitions in Sub-Saharan Africa, and post-regime change in Afghanistan and Iraq in the new century, showed that authoritarian regimes\u2019crises can lead to further instability. Through a newly-compiled database of political transitions and crises embracing the period 1975\u20132009, this contribution shows the relative impact of domestic social, economic and political factors, as well the role of international action. The piece also contributes to the analysis of\u2018stability\u2019through a macro, large-N perspective, fostering dialogue between qualitative and quantitative research agendas on the topic