A Glycine Zipper Motif Mediates the Formation of Toxic Beta-Amyloid Oligomers in Vitro and in Vivo

Background: The b-amyloid peptide (Ab) contains a Gly-XXX-Gly-XXX-Gly motif in its C-terminal region that hasbeen proposed to form a “glycine zipper” that drives the formation of toxic Ab oligomers. We have tested thishypothesis by examining the toxicity of Ab variants containing substitutions in this motif using a neuronal cell line,primary neurons, and a transgenic C. elegans model.Results: We found that a Gly37Leu substitution dramatically reduced Ab toxicity in all models tested, as measuredby cell dysfunction, cell death, synaptic alteration, or tau phosphorylation. We also demonstrated in multiplemodels that Ab Gly37Leu is actually anti-toxic, thereby supporting the hypothesis that interference with glycinezipper formation blocks assembly of toxic Ab oligomers. To test this model rigorously, we engineered second sitesubstitutions in Ab predicted by the glycine zipper model to compensate for the Gly37Leu substitution andexpressed these in C. elegans. We show that these second site substitutions restore in vivo Abtoxicity, furthersupporting the glycine zipper model.Conclusions: Our structure/function studies support the view that the glycine zipper motif present in the Cterminalportion of Ab plays an important role in the formation of toxic Ab oligomers. Compounds designed tointerfere specifically with formation of the glycine zipper could have therapeutic potential

Trashcano:Developing a quantitative teaching tool to understand ballistics accelerated by explosive volcanic eruptions

Accurate predictions of volcanological phenomena, such as the trajectory of blocks accelerated by volcanic explo-sions, require quantitative skills training. Large outdoor experiments can be useful to convey concepts of volcanicprocesses to students in an exciting way. Beyond the fun aspects, these experiments provide an opportunity toengage with the physics of projectile flight and help promote mathematical learning within the Earth Sciences.We present a quantitative framework required to interpret ballistic trajectories and the outdoor experiment knowncommonly as “trashcano”, taking a step-by-step approach to the physics of this problem, and deriving a rangeof mathematical solutions involving different levels of complexity. Our solutions are consistent with the predic-tions from established computer programs for volcanic ballistic trajectory modelling, but we additionally providea nested set of simplified solutions, useful for a range of teaching scenarios as well as downloadable simulateddatasets for use where the full experiment may not be possible