Determining the potency of neuromuscular blockers: are traditional methods flawed?
The ED(50) is a very robust parameter. When comparing the potency of neuromuscular blockers, it is this value rather than the ED(95) that should be used. The CL for the ED(95), regardless of how it is calculated, are so wide that this parameter must be viewed, at best, as an approximation.
We demonstrate for the first time that insertion of fibril-forming motifs can replace PHF6/PHF6* motifs, driving human Tau protein to form fibrils with different morphologies and different kinetic parameters. Our results suggest that fibril-forming motifs play a key role in the fibrillization of human Tau protein and could be the determinants of amyloidogenic proteins tending to misfold, thereby causing the initiation and development of neurodegenerative diseases. Our study also touches on the importance of amyloid "strains": changes to the amyloidgenic driver region results in altered structural morphologies at the macromolecular level.