No abstract

Nitric oxide (NO) is an essential signaling molecule for neurotransmission, cardiovascular function, and cellular defense. However, NO overproduction from neuronal nitric oxide synthase (nNOS) increases infarct size after ischemic stroke and has been linked to the pathogenesis of Alzheimer's and Parkinson's disease. Despite fundamental roles of NO in cellular signaling and disease, intact nNOS holoenzyme structures have remained elusive, and the structural basis for the electron transfer cycle across the reductase and oxygenase domains is unclear. In previous studies, we used negative-stain electron microscopy (EM) to determine conformational states and the overall domain organization of nNOS during its catalytic cycle. In current work, we have interrogated the nNOS and nNOS:Calmodulin (nNOS:CaM) complexes by cryogenic-EM (cryo-EM). In these intact complexes, the oxygenase dimer structure was determined to $4Å , revealing its active-state architecture, while the nNOS reductase domains were identified to be flexibly linked in both CaM-free and CaM-bound states. Additional structural analysis of crosslinked-stabilized complexes, including 2D and 3D classification, will be presented that reveals the overall architecture and highlights the use of cryo-EM methods in elucidating different conformations of the nNOS:CaM complex.

No abstract

The increasing social and environmental impacts of the textile and garment supply chain are well known and have resulted in the development of an array of initiatives, tools and assessment platforms to enhance the sustainability of the sector. There is a great deal of diversity in these initiatives, including differences in their focus, the actors involved, who the beneficiaries are, the longevity of the activities and how they define and measure success. The paper highlights where there might be gaps in the current offerings of initiatives, and what types of initiatives have alignment with MSMEs knowledge and learning needs, as a way to highlight where future attention in developing new or enhanced initiatives might lie.