Citations

Significance We identified a one-of-a-kind duplication mutation in human transthyretin (TTR) that causes unusually aggressive systemic amyloidosis. To understand the poor response to treatment with a drug that stabilizes the TTR tetramer, we explored the structure, stability, and drug binding of recombinant proteins. The results suggested that amyloid formation could stem from global destabilization of the monomeric and tetrameric protein as well as the local disordering near the mutation site. This disordering induced proteolysis with release of aggregation-prone fragments. Alternatively, local disordering could trigger misfolding of the full-length protein by exposing an adhesive segment. Drug binding at a dimer interface distant from the mutation site did not significantly influence these pathological processes, indicating the need for alternative therapeutic targets.

Immigrants and refugees arrive to the United States healthier than the general population, but this advantage declines with increasing duration of residence. One factor contributing to this decline is suboptimal physical activity, but reasons for this are poorly understood. Persons from Somalia represent the largest African refugee population to the United States, yet little is known about perceptions of physical activity among Somali men. Somali members of a community-based participatory research partnership implemented three age-stratified focus groups and three semistructured interviews among 20 Somali men in Rochester, Minnesota. Team-based inductive analysis generated themes for barriers and facilitators to physical activity. Barriers to physical activity included less walking opportunities in the United States, embarrassment about exercise clothing and lack of familiarity with exercise equipment/modalities, fear of harassment, competing priorities, facility costs, transportation, and winter weather. Facilitators to physical activity included high knowledge about how to be active, success stories from others in their community as inspiration, and community cohesion. Findings may be used to derive interventions aimed to promote physical activity among Somali men in the United States.