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Chinese and Japanese Public Opinion Searching for Moral Security
Mindy L. Kotler,Naotaka Sugawara,Tetsuya Yamada 경남대학교 극동문제연구소 2007 ASIAN PERSPECTIVE Vol.31 No.1
Japanese and Chinese hold strikingly similar opinions of each other—both are negative. Since the normalization of Japan’s postwar relations with China in 1978, opinion surveys document a clear deterioration of goodwill after nearly two decades of relatively good relations. This trend has accelerated over the past ten years. Most noticeable is how much the decline of trust coincides with a rise of internal socio-economic anxieties in both countries. The central governments are faltering in their ability to provide social stability and cohesion—a sense of safety and material well-being—while establishing a sense of national identity. We argue that current Sino-Japanese tensions reflect more each country’s domestic stresses than they do disagreements over history, any inherent geostrategic competition, or regional economic rivalry. Restoration, or the establishment of prosperity, social certainty, and “moral security” in both countries, is necessary before China and Japan can have any meaningful resolution of their historical and geopolitical issues.
Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation
Sciacca, Michele F.M.,Kotler, Samuel A.,Brender, Jeffrey R.,Chen, J.,Lee, D.k.,Ramamoorthy, A. Biophysical Society ; Published for the Biophysica 2012 Biophysical journal Vol.103 No.4
Disruption of cell membranes by Aβ is believed to be one of the key components of Aβ toxicity. However, the mechanism by which this occurs is not fully understood. Here, we demonstrate that membrane disruption by Aβ occurs by a two-step process, with the initial formation of ion-selective pores followed by nonspecific fragmentation of the lipid membrane during amyloid fiber formation. Immediately after the addition of freshly dissolved Aβ<SUB>1-40</SUB>, defects form on the membrane that share many of the properties of Aβ channels originally reported from single-channel electrical recording, such as cation selectivity and the ability to be blockaded by zinc. By contrast, subsequent amyloid fiber formation on the surface of the membrane fragments the membrane in a way that is not cation selective and cannot be stopped by zinc ions. Moreover, we observed that the presence of ganglioside enhances both the initial pore formation and the fiber-dependent membrane fragmentation process. Whereas pore formation by freshly dissolved Aβ<SUB>1-40</SUB> is weakly observed in the absence of gangliosides, fiber-dependent membrane fragmentation can only be observed in their presence. These results provide insights into the toxicity of Aβ and may aid in the design of specific compounds to alleviate the neurodegeneration of Alzheimer's disease.
Lee, Dong-Kuk,Bhunia, Anirban,Kotler, Samuel A.,Ramamoorthy, Ayyalusamy American Chemical Society 2015 Biochemistry Vol.54 No.10
<P>Multidrug resistance against the existing antibiotics is becoming a global threat, and any potential drug that can be designed using cationic antimicrobial peptides (AMP) could be an alternate solution to alleviate this existing problem. The mechanism of action of killing bacteria by an AMP differs drastically in comparison to that of small molecule antibiotics. The main target of AMPs is to interact with the lipid bilayer of the cell membrane and disrupt it to kill bacteria. Consequently, the modes of membrane interaction that lead to the selectivity of an AMP are very important to understand. Here, we have used different membrane compositions, such as negatively charged, zwitterionic, or mixed large unilamellar vesicles (LUVs), to study the interaction of four different synthetically designed cationic, linear antimicrobial peptides: MSI-78 (commercially known as pexiganan), MSI-367, MSI-594, and MSI-843. Our solid-state nuclear magnetic resonance (NMR) experiments confirmed that the MSI peptides fragmented LUVs through a detergent-like carpet mechanism depending on the amino acid sequence of the MSI peptide and/or the membrane composition of LUVs. Interestingly, the fragmented lipid aggregates such as SUVs or micelles are sufficiently small to produce an isotropic peak in the <SUP>31</SUP>P NMR spectrum. These fragmented lipid aggregates contain only MSI peptides bestowed with lipid molecules as confirmed by NMR in conjunction with circular dichroism spectroscopy. Our results also demonstrate that cholesterol, which is present only in the eukaryotic cell membrane, inhibits the MSI-induced fragmentation of LUVs, suggesting that the MSI peptides can discriminate the bacteria and the eukaryotic cell membranes, and this selectivity could be used for further development of novel antibiotics.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/2015/bichaw.2015.54.issue-10/bi501418m/production/images/medium/bi-2014-01418m_0013.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bi501418m'>ACS Electronic Supporting Info</A></P>