Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2′-modified-4′-thionucleosides

AbstractGene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a ‘target domain’ and a ‘U1 domain’, we prepared adaptor ONs using 2′-modified-4′-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2′-fluoro-4′-thionucleoside and 2′-fluoronucleoside units as well as only 2′-fluoronucleoside units, while those prepared as combination of 2′-OMe nucleoside/2′-OMe-4′-thionucleoside and 2′-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity

Inter-rater reliability of streetscape audits using online observations: Microscale Audit of Pedestrian Streetscapes (MAPS) global in Japan

This study aimed to evaluate the inter-rater reliability of streetscape audits among online observations using the Microscale Audit of Pedestrian Streetscapes-Global version (MAPS-Global) in Japan. MAPS-Global observations were conducted on routes with distances ranging from 400 to 725 m from a residence toward a non-residential destination. Google Street View audits were independently conducted by two trained raters on each route. A tiered scoring system was applied to summarize the items at multiple levels of aggregation. Positive and negative valence scores were created based on the expected association with physical activity. Inter-rater reliability analyses were performed using kappa statistics or intraclass correlation coefficients (ICC). Of the 32 older adults participating in an intervention study in the community-wide physical activity promotion project in Fujisawa City, 19 addresses were used, excluding those with nearby addresses. Results demonstrated “excellent” agreement for most of the summary scores analyzed (kappa or ICC values of 0.75 or higher [80.4 %]), while 6.5 % of items exhibited “good” agreement (ICC = 0.60–0.74). By contrast, only 13.0 % of the scales had ICC values lower than 0.60 (“fair” or “poor” reliability). The results illustrated high reliability for the grand summary scores and composite subscale measures. However, caution should be exercised when interpreting subscale scores for less frequently observed negative attributes and aesthetic/social characteristics. The results presented in this study support the application of online observations using MAPS-Global in urban areas of Japan, which could be implemented to inform decisions related not only to physical activity but also to traffic safety

Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2'-modified-4'-thionucleosides

Gene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a ‘target domain’ and a ‘U1 domain’, we prepared adaptor ONs using 2'-modified-4'-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2'-fluoro-4'-thionucleoside and 2'-fluoronucleoside units as well as only 2'-fluoronucleoside units, while those prepared as combination of 2'-OMe nucleoside/2'-OMe-4'-thionucleoside and 2'-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity

Psychological Aspects of Students\u27Life in a High School with a Credit System and No Grade System (2) : Five Case Studies Based on the Results of an Interview Survey

This is a case study of students\u27growth processes in a senior high school with a credit system and no grade system. The credit-system high school has been founded to take in high school dropouts and truants. In this study, the interviews were used to assess how students\u27daily school experiences influence the processes and the mechanisms of students\u27growth. The findings revealed that the flexible system encourages a huge variety of students to grow up in various manners. Not only those who exercise their autonomy but also those who lack self-direction can make good use of the system and grow up in the high school. As a result, many dropouts and truants are able to return to school