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For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

This book presents pioneering work on an interregional input-output table of the Chinese economy and its applications to the analysis of interregional and interindustrial relations in China. It is the fruit of the authors' joint efforts of more than five years to establish a solid basis for the analysis of interregional relations in China, in the hope of laying the foundation for further studies of regional development in that country. The book endeavors to make a contribution to the regional typology of the Chinese economy. The Chinese provinces are classified into seven large regions. The interregional input-output table is constructed accordingly. Chapter I describes the methodology for producing this interregional input-output (IRIO) table. Chapter II presents the (IRIO) table after a brief explanation of the Chinese statistical data needed for the compilation of the table. Chapter III explains the basis of seven large regions adopted for the IRIO table. Chapter IV deals with the interdependence of regions and the effects of the changes in some parameters of one region on the activities in other regions. Chapter V, the last chapter, applies the IRIO table to policy analysis.

This book explores the important topic of fiscal decentralization in Asian countries, and focuses on how government finance and administration are being reformed to bring budgetary decisions closer to voters.

This book offers the representative macroeconometric models and their applications for the Japanese economy in different development stages throughout the postwar years up to the present. It presents a summary of three types of macroeconometric models and analyses: -Social accounting analyses of national income and related indices — following the tradition of C Clark, S Kuznets, R Stone and World Bank Development Reports; -Inter-industrial and inter-regional analyses of the Japanese economy a la W Leontief and the CGE (computable general equilibrium) type of applications to Comprehensive Development Plans; -Macroeconometric model building for the Japanese economy and its applications with a survey of various models in Japan, including the historic Osaka University ISER (Institute of Social and Economic Research) model and present day Government models.

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress. Liquid-liquid phase separation of p62/SQSTM1 has been previously described, although the significance in vivo remains unclear. Here the authors show p62 droplets contain ubiquitin, autophagy-related proteins and Keap1 to serve as platform of not only autophagosome formation but also Nrf2 activation.

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy- cis -12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus -colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites. The gut microbiome is an important regulator of metabolic health. Here the authors show that intestinal bacteria metabolize dietary linoleic acid to 10-hydroxy- cis -12-octadecenoic acid (HYA) which confers host resistance to high fat diet-induced obesity in mice.