Endosomal Escape of Peptide-Photosensitizer Conjugates Is Affected by Amino Acid Sequences near the Photosensitizer.

Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of peptides and proteins, but CPP fusion peptides and proteins are often transported by endocytosis and trapped in endosomes. Photochemical internalization (PCI) is a method for the endosomal escape of the trapped peptide or protein and release into the cytosol using light and photosensitizers. In PCI, endosomal membranes are thought to be destabilized by singlet oxygen (1O2) photogenerated from photosensitizers localized in endosomes. We previously developed CPP-cargo-photosensitizer (PS) conjugates able to photodependently enter the cytosol via the PCI mechanism. For example, TatU1A-PS (a covalent complex of Tat [CPP], U1A RNA-binding protein [cargo], and PS) can photodependently deliver RNAs into the cytosol, and TatBim-PS (a covalent complex of Tat, Bim [cargo], and PS) can photoinduce apoptosis in mammalian cells. However, for many newly created conjugates, the induction of PCI has been insufficient. We hypothesized that the amino acid linker sequence (XX) adjacent to the photosensitizer is an important determinant of PCI efficiency. In this study, using CPP-cargo-XX-PS platforms, we examined the relationship between PCI efficiency and the linker amino acid sequence near the photosensitizer. We found that hydrophobic FF and LL linkers enhanced the PCI efficiencies of both TatBim-XX-PS and TatU1A-XX-PS. The effectiveness of the linker depended, in part, on both the cargo moiety and the photosensitizer. These results may guide the design of CPP-cargo-PS conjugates conferring broad target functions for PCI and photodynamic therapy.

Implementation and experiments for interactive lyrics transcreation system.

The evolution of the Internet has enabled us to enjoy the music created in various countries. But still, it is often difficult to understand the lyrics written in foreign languages. Professional translators have published many international songs with lyrics that fit the melody so that the ordinary people can enjoy the lyrics of such international songs. This paper discusses lyrics transcreation into the Japanese language. Also, the paper presents an interactive visual lyrics transcreation system and describes the details of its implementation. This system allows users to select temporary lyrics from a set of tentative translations and then freely modify the lyrics with a real-time visualization mechanism. We also propose a lyrics translation algorithm that solves an essential problem of lyrics translation into Japanese. In this study, we interviewed two experts regarding problems with lyrics translation and received reviews of our presented system. We also conducted preliminary experiments with 19 participants to determine the best combination of user interface components for our system. We performed additional user experiments inviting 12 participants to compare lyrics transcreation using the presented system to manual lyrics transcreation. Lyrics transcreation by the presented system brought better results against those of manual transcreation.