Structural basis of insulin fibrillation.

Insulin is a hormone responsible for maintaining normal glucose levels by activating insulin receptor (IR) and is the primary treatment for diabetes. However, insulin is prone to unfolding and forming cross-ß fibers. Fibrillation complicates insulin storage and therapeutic application. Molecular details of insulin fibrillation remain unclear, hindering efforts to prevent fibrillation process. Here, we characterized insulin fibrils using cryo-electron microscopy (cryo-EM), showing multiple forms that contain one or more of the protofilaments containing both the A and B chains of insulin linked by disulfide bonds. We solved the cryo-EM structure of one of the fibril forms composed of two protofilaments at 3.2-Å resolution, which reveals both the ß sheet conformation of the protofilament and the packing interaction between them that underlie the fibrillation. On the basis of this structure, we designed several insulin mutants that display reduced fibrillation while maintaining native IR signaling activity. These designed insulin analogs may be developed into more effective therapeutics for type 1 diabetes.

Toward a model of curriculum analysis and evaluation - Beka: a case study from Australia.

All curricula vary in the way that it is constructed, implemented and experienced. Regardless of the context, ongoing evaluation of learning objectives, processes and content within curriculum is critical. Based primarily on the work of Glatthorn (1987), Print (1993) and Reid (2005), this paper describes a case study of an undergraduate nursing curriculum. The analysis described in this paper forms the basis of a process incorporating four key steps: benchmarking, evidencing, knowing and applying (BEKA). By critiquing the literature, and explaining the merge of others' processes and models of curriculum analysis, it is argued that the BEKA framework of curriculum analysis forms a useful and powerful tool enabling understanding of the actual process of teaching, coverage of curriculum content and assessment, and demonstrating linkages between theory and practice.