Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.

Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity.

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As the platform business becomes more important, it is crucial to make adequate decisions and choices for strategies, considering influence factors in relation to the platform for each growth model. This study researched how to build a platform business in the IT industry from the perspective of a dynamic approach to understand how the platform growth model successfully enables business entities to enter the market and to continue expansion. Through 21 case studies, this research formulated the four stages of platform growth model: entry, growth, expansion and maturity, providing a conceptual framework to build a platform growth model ecosystem.

The purpose of this study is to explore the relationships between three intangible resources and the innovation performance of Chinese high-tech firms, and the moderating effect of internationalization on these relationships. We implement a hierarchical multiple regression analysis using data for 274 Chinese high-tech firms. The results show that all three intangible resources, measured by top management team diversity, research and development intensity, and government subsidies, positively influence Chinese high-tech firm innovation performance. We find the relationships between these intangible resources and the innovation performance of Chinese high-tech firms are significantly positively moderated by internationalization. These findings have important implications, as follows. First, they provide evidence of the strategic value of intangible resources and their effects on innovation performance. Second, our results show that increasing internationalization alone does not guarantee performance improvement. Firms should consider their internal and external environments and the complex relationships among factors when they make decisions about internationalization investments. Prior research does not provide an explanation for how internationalization affects performance, because it primarily focuses on the direct relationship between internationalization and performance. This study overcomes this limitation by examining the indirect effect of internationalization on performance.