Structure and dynamics of the active Gs-coupled human secretin receptor

The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD

The search for standard costing in the United States and Britain

This article describes the relationship between the understanding and practice of standard costing in both the U.S. and the U.K. and discusses the development of specific practices in the immediate post-World War II period. Based on a detailed review of the post-war literature, the authors conclude that the quantity and quality of standard costing and related scientific management practices (time study, variance analysis, etc.) reached a level in practice that many accounting historians have felt should have been achieved at an earlier point in time. Another principal finding is that standard costing, initially promulgated in the late 1910s, continued to develop in both the U.S. and the U.K. in evolutionary fashion into the late 1940s and 1950s, a finding which demonstrates that Britain was not as far behind America in terms of its standard costing practices as has been commonly believed. The article also explicates the relatively minor impact of the Anglo-American Council on Productivity, sponsor of sixty-six post-war visitations over a four-year period by British groups of employers, trade unionists and professionals, to study American industrial methods, including standard costing

The economic impact of Scottish salmon farming

SIGLEAvailable from British Library Document Supply Centre-DSC:3654.4795(7) / BLDSC - British Library Document Supply CentreGBUnited Kingdo