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N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or...
The knowledge base required to diagnose and treat cardiovascular disease (CVD) is large and rapidly expanding, although the amount of time available to physicians and other health care providers to acquire this information is finite and shrinking. As clinicians, we are required to triage new information with respect to its importance and value to our clinical mission and to the time and effort required...
Cardiovascular disease (CVD) remains the most common cause of mortality in the United States. The emphasis on prevention, early detection, and recent advents in pharmacological and interventional approaches has resulted in significant reduction in the associated mortality and morbidity. There is widespread public interest in the use of alternative medicine to prevent and treat these diseases. The...
With more than 50% of patients self-medicating today and with the enormous variety of complementary or alternative medicines (CAM) available, it has become imperative for health care providers to be familiar with, and knowledgeable about, these widely used treatments. In Complementary and Alternative Cardiovascular Medicine, academic clinicians, clinical scientists, well-known practitioners of alternative...
Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNaV) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNaV CTD exerts a profound influence on gating through a temperature-dependent unfolding transition...
Escherichia coli 5′-nucleotidase is a two-domain enzyme exhibiting a unique 96° domain motion that is required for catalysis. Here we present an integrated structural biology study that combines DEER distance distributions with structural information from X-ray crystallography and computational biology to describe the population of presumably almost isoenergetic open and closed states in solution...
Nitroxide spin labels are used for double electron-electron resonance (DEER) measurements of distances between sites in biomolecules. Rotation of gem-dimethyls in commonly used nitroxides causes spin echo dephasing times (Tm) to be too short to perform DEER measurements at temperatures between ∼80 and 295 K, even in immobilized samples. A spirocyclohexyl spin label has been prepared that has longer...
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