Basic Science and Pathogenesis.

Background: APOE4 carriers exhibit cerebrovascular dysfunction which may contribute to the development of cognitive decline and dementia; however, the mechanisms underlying this pathophysiology remain unknown. Impaired cerebrovascular reactivity (CVR) may be associated with vascular injury, inflammation, and endothelial dysfunction. To examine whether these processes may be involved in CVR deficits in APOE4 carriers, we explored whether plasma levels of vascular injury markers indicative of inflammation and endothelial dysfunction are associated with impaired CVR to hypercapnia and hypocapnia in older APOE4 carriers.

Effects of macro vs. micro initialization and ocean initial-condition memory on the evolution of ensemble spread in the CESM2 large ensemble.

Unlabelled: "Single Model initial-condition Large Ensembles" (SMILEs) conducted with Earth system models have transformed our ability to quantify internal climate variability and forced climate change at local and regional scales. An important consideration in their experimental design is the choice of initialization procedure as this influences the duration of initial-condition memory, with implications for interpreting the temporal evolution of both the ensemble-mean and ensemble-spread. Here we leverage the strategic design of the 100-member Community Earth System Model version 2 (CESM2) SMILE to investigate the dependence of ensemble spread on the method of initialization (micro- vs.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Introduction: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: One hundred sixty-one older adults free of dementia or major neurological/psychiatric disorders were recruited.

A comprehensive review of the proline mimic azetidine-2-carboxylic acid (A2C).

The imino acid azetidine-2-carboxylic acid (A2C), a proline homologue, was first identified in liliaceous plants in 1955. Its ability to exchange for proline in protein synthesis is responsible for its teratogenic effects and has made it a very useful tool for generating non-native proteins to study proteotoxic stress and ER stress. The tRNA synthetases from some A2C-producing plants can discriminate between proline and A2C, but for most plants and for mammalian cells, A2C is mistakenly used in protein synthesis in place of proline and can avoid cell proof-reading mechanisms.