Domino Alkene-Isomerization–Claisen Rearrangement Strategy to Substituted Allylsilanes

A one-pot isomerization–Claisen protocol has been developed for the synthesis of highly substituted allylsilanes. Monosilylated divinyl ethers can be isomerized using a cationic iridium(I) catalyst followed by a thermal Claisen rearrangement to provide the allylsilanes in excellent yields and diastereoselectivities.

A novel dual-fluorescence strategy for functionally validating microRNA targets in 3-prime untranslated regions: regulation of the inward rectifier potassium channel Kir2.1 by miR-212.

Gene targeting by microRNAs is important in health and disease. We developed a functional assay for identifying microRNA targets and applied it to the K+ channel Kir2.1 (KCNJ2) which is dysregulated in cardiac and vascular disorders. The 3'UTR was inserted downstream of the mCherry red fluorescent protein coding sequence in a mammalian expression plasmid. MicroRNA sequences were inserted into the pSM30 expression vector which provides enhanced green fluorescent protein as an indicator of microRNA expression. HEK293 cells were co-transfected with the mCherry-3'UTR plasmid and a pSM30-based plasmid with a microRNA insert. The principle of the assay is that functional targeting of the 3'UTR by the microRNA results in a decrease in the red/green fluorescence intensity ratio as determined by automated image analysis. The method was validated with miR-1, a known downregulator of Kir2.1 expression, and was used to investigate targeting of the Kir2.1 3'UTR by miR-212. Red/green ratio was lower in miR-212-expressing cells compared to non-targeting controls, an effect that was attenuated by mutating the predicted target site. MiR-212 also reduced inward rectifier current and Kir2.1 protein in HeLa cells. This novel assay has several advantages over traditional luciferase-based assays including larger sample size, amenability to time course studies and adaptability to high-throughput screening.

Reintegrative and Disintegrative Shaming:Legal and Ethical Issues

Abstract
This chapter considers a range of legal and ethical issues raised by the use of reintegrative and disintegrative shaming techniques (Braithwaite, 1989) with sex offenders. ‘Disintegrative shaming’ labels and stigmatises offenders, ostracises them from the local community and may result in violence directed towards offenders (McAlinden, 2005, 2007). ‘Reintegrative shaming’, on the other hand, focuses on rehabilitating the offender within a supportive community environment and assisting the offender in their efforts to change. The former is evident in the range of recent legislative responses designed to protect the community from sex offenders such as notification as well as the popular demand for measures which ‘name and shame’ known sex offenders. The latter is more clearly related to restorative measures such as circles of support and accountability. This chapter argues that although traditionally at opposite ends of the intervention spectrum, each type of mechanism gives rise to potentially difficult legal and ethical considerations.