The Relevance of Religious Freedom

This Education Week fireside address was given to the J. Reuben Clark Law Society at Brigham Young University on August 21, 2007

The Role of Law and Lawyers in Japan and the United States

The issues raised in connection with delivery of legal services in Japan are complex and best understood against the backdrop of the development of the legal profession in Japan. Part I of this article discusses the history of the Japanese legal profession, especially its recent history. Part II shows how this development has shaped the issues in the current dispute. It recounts the development of the dispute, the arguments that have been made on the Japanese and American sides, and the course of the negotiations over legal services as part of the Japan-U.S. trade agenda. This article concludes with a critical analysis of the recent Japanese proposals for regulating foreign legal consultants

A microfluidic architecture with multidirectional diffusion for modelling the stromal compartment of pancreatic ductal adenocarcinoma

Please click Download on the upper right corner to see the full descriptio

Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells.

A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by alterations in the redox state of critical thiols in the IP3R, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We found that under basal conditions, ∼5 of the 60 cysteines are oxidized in IP3R1. Cell treatment with 50 μm thimerosal altered gel shifts, indicating oxidation of ∼20 cysteines. By contrast, the shifts induced by 0.5 mm H2O2 or other oxidants were much smaller. Monitoring of biotin-maleimide attachment to IP3R1 by LC-MS/MS with 71% coverage of the receptor sequence revealed modification of two cytosolic (Cys-292 and Cys-1415) and two intraluminal cysteines (Cys-2496 and Cys-2533) under basal conditions. The thimerosal treatment modified an additional eleven cysteines, but only three (Cys-206, Cys-767, and Cys-1459) were consistently oxidized in multiple experiments. H2O2 also oxidized Cys-206 and additionally oxidized two residues not modified by thimerosal (Cys-214 and Cys-1397). Potentiation of IP3R channel function by oxidants was measured with cysteine variants transfected into a HEK293 IP3R triple-knockout cell line, indicating that the functionally relevant redox-sensitive cysteines are predominantly clustered within the N-terminal suppressor domain of IP3R. To our knowledge, this study is the first that has used proteomic methods to assess the redox state of individual thiols in IP3R in intact cells. © 2018 Joseph et al