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Calcium-Mediated Induction Of Vibrio Fischeri Es114 Biofilms, Katia Elizabeth Semenchuk

Master's Theses

Vibrio fischeri bacteria form biofilms that facilitate symbiotic colonization of the Hawaiian bobtail squid, Euprymna scolopes. These host-associated biofilms require production of the SYP polysaccharide. However, it has been difficult to observe robust biofilm formation in vitro in a laboratory setting using wild-type strain ES114; instead, most work investigating syp-dependent biofilm formation has relied on genetically altered strains. Guided by recent findings that increasing calcium induces c-di-GMP (Tischler et al., 2021), a molecule known in other systems to promote biofilm formation, the question was posed as to whether high levels of calcium alone could promote syp-dependent biofilm formation by ES114. …

A Discrete Loop In Serca N-Domain Plays A Role In Serca Headpiece Dynamics And Function, Olga N. Raguimova

Dissertations

The sarco/endoplasmic reticulum calcium ATPase (SERCA) is the major regulator of Ca2+ levels in the cell. Deficient calcium handling in the heart has been linked to heart failure, a leading cause of death in developed countries. As of today, targeting SERCA to enhance cardiac function has not been successful due to lack of details about SERCA structural dynamics during Ca2+ transport.

In my research, I utilized MD simulations and variety of physical assays to determine the role of Nβ5-β6 loop in regulation of SERCA structural dynamics during Ca2+ transport. Previous MD simulations by our lab predicted that the Nβ5-β6 loop …

Kv7 K+ Channels In Airway Smooth Muscle Cells As Target For Asthma Therapy, Priyanka Prakash Kakad

Master's Theses

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor …

An Investigation Of The Phospholamban-Serca Regulatory Interaction With Fluorescence Resonance Energy Transfer, Philip Adam Bidwell

Dissertations

With Fluorescence Resonance Energy Transfer (FRET), we are able to detect changes in the structure and affinity of the PLB-SERCA regulatory complex in live cells. Using this approach, we have detected a high level of PLB-SERCA interaction even at Ca2+ concentrations known to fully relieve PLB inhibition of SERCA, suggesting that dissociation is not required for relief of inhibition. We also detect no real-time change in PLB-SERCA binding over the course of a single Ca2+ transient in paced myocytes. The effect of Ca2+ on the PLB-SERCA interaction is best described as a reduced affinity with no change in the structure …

Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, Sahadev A. Shankarappa

Dissertations

Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 …

Regulation Of Transglutaminase By 5-Ht2a Receptor Signaling And Calmodulin, Ying Dai

Dissertations

Transglutaminase (TGase), nature’s biological glue, catalyzes the post-translational modification of proteins by formation of intra- and intermolecular protein cross-links or by primary amine incorporation. TGase has various physiological functions, such as skin-barrier formation and blood clot stabilization, whereas increasing evidence indicates they may also involved in neurodegenerative diseases including Huntington’s disease (HD), Alzheimer disease’s, and progressive supranuclear palsy. Mutant huntingtin (htt) and small G proteins (e.g. Rac 1) are potential substrates of TGases. The purpose of this dissertation was to characterize the mechanisms by which 5-HT2A receptor signaling and calmodulin (CaM) regulate TGase-catalyzed transamidation of Rac1 and htt in cultured …