Improved split fluorescent proteins for endogenous protein labeling.

Self-complementing split fluorescent proteins (FPs) have been widely used for protein labeling, visualization of subcellular protein localization, and detection of cell-cell contact. To expand this toolset, we have developed a screening strategy for the direct engineering of self-complementing split FPs. Via this strategy, we have generated a yellow-green split-mNeonGreen21-10/11 that improves the ratio of complemented signal to the background of FP1-10-expressing cells compared to the commonly used split GFP1-10/11; as well as a 10-fold brighter red-colored split-sfCherry21-10/11. Based on split sfCherry2, we have engineered a photoactivatable variant that enables single-molecule localization-based super-resolution microscopy. We have demonstrated dual-color endogenous protein tagging with sfCherry211 and GFP11, revealing that endoplasmic reticulum translocon complex Sec61B has reduced abundance in certain peripheral tubules. These new split FPs not only offer multiple colors for imaging interaction networks of endogenous proteins, but also hold the potential to provide orthogonal handles for biochemical isolation of native protein complexes.Split fluorescent proteins (FPs) have been widely used to visualise proteins in cells. Here the authors develop a screen for engineering new split FPs, and report a yellow-green split-mNeonGreen2 with reduced background, a red split-sfCherry2 for multicolour labeling, and its photoactivatable variant for super-resolution use

Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case-control study

Ikeda, S, Ueda, Y, Hara, M, et al. Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case‐control study. Cancer Sci. 2020; 00: 1– 8. https://doi.org/10.1111/cas.14682

Epidemiologic profile of type-specific human papillomavirus infection after initiation of HPV vaccination

Funding Information: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103]. Acknowledgments: We would like to thank Yuka Watanabe, Sachiko Ono, Anna Ishida, Yoko Motoki and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD

Japan's Ongoing Crisis on HPV Vaccination.

Funding: This work was supported by the Health and Labor Sciences Research Grant [26272001] and the Japanese Agency for Medical Research and Development [JP15ck0106103]. Acknowledgments: We would like to thank Yuka Watanabe, Sachiko Ono, Anna Ishida, Yoko Motoki, Tomomi Egawa-Takata, Akiko Morimoto, Yusuke Tanaka and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD

Long-term effectiveness of HPV vaccination against HPV infection in young Japanese women : Real-world data.

ACKNOWLEDGEMENTS We would like to thank Ms. Yuka Watanabe, Ms. Sachiko Ono, Ms. Anna Ishida, and the administrator of Niigata city for their support in conducting the surveyPeer reviewedPublisher PD

Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data : A Systematic Review

Peer reviewedPublisher PD

Effectiveness of human papillomavirus vaccine against cervical precancer in Japan : Multivariate analyses adjusted for sexual activity.

ACKNOWLEDGMENTS We would like to thank Mr Kenshin Sekine and Mr Taishin Sekine for English editing, and Ms Yuka Watanabe, Ms Sachiko Ono, Ms Anna Ishida, and administrators of Niigata, Nagaoka, Joetsu, Shibata, Sanjo, Mitsuke city for their support in conducting the survey.Peer reviewedPublisher PD

The role of mother's acting behavior and questioning druing picture-book reading in infancy: An examination of the emotional effect of such behavior on mother-child

This study examines whether “mother’s acting behavior (imitating characters in a picture-book of onomatopoeia) and questioning (questioning the child about a picture-book) promotes the expression of emotions during mother-child interactions. In this study, the participants were 5 mother-child dyads (3 boys and 2 girls). Researchers observed a scene of picture-book reading every month, and calculated rate of appearance of mother –child behaviors. The observation period was from the 6 month since the birth of the child until the 24 month. The “mother’s acting behavior” was associated with the rate of the child’s interaction with the picture-book, such as touching a picture and non-verbal utterances. Furthermore, questioning was associated with the number of times a child pointed at the book, uttered a meaningful word, or imitated a character from the book. Results show that the mother’s acting behavior promoted non-verbal mother-child interaction from the age of 7 month, and questioning promoted verbal communication between mother and child after the child was 11 months old. It is assumed that non-verbal communication between mother and child during infancy encourages positive emotional interaction. Furthermore, it is revealed that mother used behavior properly in association with a degree of child’s development

Role of conserved arginine in the heme distal site of HutZ from Vibrio cholerae in the heme degradation reaction

HutZ from Vibrio cholerae is a dimeric enzyme that catalyzes degradation of heme. The highly conserved Arg92 residue in the HutZ family is proposed to interact with an iron-bound water molecule in the distal heme pocket. To clarify the specific role of Arg92 in the heme degradation reaction, the residue was substituted with alanine, leucine, histidine or lysine to modulate electrostatic interactions with iron-bound ligand. All four Arg92 mutants reacted with hydrogen peroxide to form verdoheme, a prominent intermediate in the heme degradation process. However, when ascorbic acid was used as an electron source, iron was not released even at pH 6.0 despite a decrease in the Soret band, indicating that non-enzymatic heme degradation occurred. Comparison of the rates of heme reduction, ligand binding and verdoheme formation suggested that proton transfer to the reduced oxyferrous heme, a potential rate-limiting step of heme degradation in HutZ, is hampered by mutation. In our previous study, we found that the increase in the distance between heme and Trp109 from 16 to 18 Å upon lowering the pH from 8.0 to 6.0 leads to activation of ascorbic acid-assisted heme degradation by HutZ. The distance in Arg92 mutants was >19 Å at pH 6.0, suggesting that subunit-subunit interactions at this pH are not suitable for heme degradation, similar to Asp132 and His63 mutants. These results suggest that interactions of Arg92 with heme-bound ligand induce alterations in the distance between subunits, which plays a key role in controlling the heme degradation activity of HutZ