Amyloid ß-Protein C-Terminal Fragments: Formation of Cylindrins and ß-Barrels.

In order to evaluate potential therapeutic targets for treatment of amyloidoses such as Alzheimer's disease (AD), it is essential to determine the structures of toxic amyloid oligomers. However, for the amyloid ß-protein peptide (Aß), thought to be the seminal neuropathogenetic agent in AD, its fast aggregation kinetics and the rapid equilibrium dynamics among oligomers of different size pose significant experimental challenges. Here we use ion-mobility mass spectrometry, in combination with electron microscopy, atomic force microscopy, and computational modeling, to test the hypothesis that Aß peptides can form oligomeric structures resembling cylindrins and ß-barrels. These structures are hypothesized to cause neuronal injury and death through perturbation of plasma membrane integrity. We show that hexamers of C-terminal Aß fragments, including Aß(24-34), Aß(25-35) and Aß(26-36), have collision cross sections similar to those of cylindrins. We also show that linking two identical fragments head-to-tail using diglycine increases the proportion of cylindrin-sized oligomers. In addition, we find that larger oligomers of these fragments may adopt ß-barrel structures and that ß-barrels can be formed by folding an out-of-register ß-sheet, a common type of structure found in amyloid proteins.

Multiorganizational Partnerships: A Mechanism for Increasing the Employment of Internationally Educated Nurses.

BACKGROUND: Internationally educated nurses (IENs) face multiple challenges in entering and integrating into the Canadian workforce. These challenges include getting to know the Canadian culture, nursing accountabilities, professional practice requirements and experience or qualifications deemed not equivalent to the Canadian standard. Hamilton Health Sciences' (HHS') IEN Integration Project has been funded by the Ontario and Canadian governments to support IENs in overcoming these challenges and contribute to the healthcare system. AIM: The aim of this article is to describe a multiorganizational project that prepares IENs for employment in Canadian healthcare. STRATEGY: HHS invited partners in education and immigrant support services to co-design the project. A community collaboration employment model (CCEM) was developed to leverage each partner's strengths in targeted interventions to address the needs of IENs, as identified in focus groups. The interventions pertain to professional practice and accountability in the Canadian healthcare setting, workplace language, communication and selected clinical skills. RESULTS: Between project initiation in 2009 and early 2021, 591 IENs obtained employment. CONCLUSION: Multiorganizational partnerships can help build and sustain a strong nursing workforce, and IENs can fill gaps in care. A needs-based approach and the CCEM increased the likelihood of IEN employment. The ability of the CCEM to engage partners makes it relevant for healthcare organizations.