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The Unconventional Amino Acid Starvation Response Of The Malaria Parasite, Plasmodium Falciparum, Shalon Ledbetter
The Unconventional Amino Acid Starvation Response Of The Malaria Parasite, Plasmodium Falciparum, Shalon Ledbetter
All Theses and Dissertations (ETDs)
The apicomplexan parasite, Plasmodium falciparum, is the causative agent of the most severe form of malaria, resulting in nearly 1 million deaths each year. The parasite establishes its replicative niche within human erythrocytes, where it degrades massive amounts of host cell hemoglobin, salvaging the released amino acids for its own use. However, human hemoglobin does not contain the amino acid isoleucine, which is one of the most prevalent amino acids in the parasite's proteome. Since P. falciparum cannot synthesize isoleucine, it must acquire this amino acid from human serum. Optimal growth and, ultimately, the survival of P. falciparum depend on …
From Bacteria To Human: Biophysical Studies Of Inward Rectifying Potassium Channels, Wayland Cheng
From Bacteria To Human: Biophysical Studies Of Inward Rectifying Potassium Channels, Wayland Cheng
All Theses and Dissertations (ETDs)
Inward rectifying potassium: Kir) channels are important in regulating cellular excitability in organs such as the heart, brain and pancreas. Prokaryotic KirBac channels are structurally similar to eukaryotic Kir channels, but distantly related and of unknown function. The goal of this thesis has been to investigate the functional properties of KirBac1.1 and to relate these findings to eukaryotic Kir channels. The approach was to use recombinantly-expressed, purified K+ channels--KirBac1.1, KcsA, Kir2.1 and Kir2.2--in order to integrate findings from functional studies, using liposomal flux assays and patch-clamping, with high-resolution crystal structures. By reconstituting KirBac1.1 into giant liposomes for patch-clamping, I show …
Cardiac Pi3kα Signaling And K+ Channel Regulation In Cardiac Hypertrophy And Heart Failure, Kai-Chien Yang
Cardiac Pi3kα Signaling And K+ Channel Regulation In Cardiac Hypertrophy And Heart Failure, Kai-Chien Yang
All Theses and Dissertations (ETDs)
Pathologic biomechanical stresses cause cardiac hypertrophy, which is associated with QT prolongation and increased risk of life-threatening ventricular arrhythmias. Previous studies demonstrated that repolarizing K+ current densities are decreased in pressure overload-induced left ventricular hypertrophy, resulting in action potential and QT prolongation. Cardiac hypertrophy also occurs with exercise training, but this "physiological hypertrophy" is not associated with electrical abnormalities or increased arrhythmia risk, suggesting that repolarizing K+ currents are upregulated, in parallel with the increase in myocyte size, to maintain normal cardiac function. To explore this hypothesis directly, two mouse models of physiological hypertrophy, one produced by chronic exercise: swim-) …
Novel Roles For A-Type Lamins In Maintaining Genomic Stability, Abena Redwood
Novel Roles For A-Type Lamins In Maintaining Genomic Stability, Abena Redwood
All Theses and Dissertations (ETDs)
A-type lamins, key structural components of the nucleus, have been implicated in the maintenance of nuclear architecture and chromatin organization. Mutations in A-type lamins have been associated with defects in a number of nuclear processes, including DNA replication and repair, and gene transcription and silencing. In support of an important role for nuclear organization in pathogenesis, mutations in A-type lamins are associated with a wide variety of degenerative diseases which range from muscular dystrophies and lipodystrophies to premature aging syndromes. In addition, alterations in the expression of A-type lamins are associated with different cancers such as small cell lung carcinoma …
Taspase1 Is A Non-Oncogene Mediator Of Tumorigenesis And Maintenance, David Chen
Taspase1 Is A Non-Oncogene Mediator Of Tumorigenesis And Maintenance, David Chen
All Theses and Dissertations (ETDs)
The clinical success of oncogene-targeted therapies substantiates the continued reliance of certain cancers upon the continued function of apical oncogenes involved in its genesis--a phenomenon known as "oncogene addiction." Though this shift from non-targeted, cytotoxic therapies offers new hope to patients, resistance to oncogene inactivation often remains an eventuality, and it is clear that further investigation is required to more effectively battle cancer using alternative therapeutic targets. Our studies on Taspase1: threonine aspartase 1) reveal its role in coordinating cellular proliferation and apoptosis in cancer. Loss of Taspase1 by shRNA-mediated knockdown decreased cellular proliferation in a diverse set of cancer …
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
All Theses and Dissertations (ETDs)
Osteoclasts are essential for skeletal homeostasis: Teitelbaum, 2000). These macrophage-lineage cells function by generating a polarized microenvironment between themselves and bone wherein skeletal matrix is degraded. This resorptive compartment is isolated from the general extracellular space by an actin ring which encompasses the ruffled border, a convoluted plasma membrane structure formed by its fusion with lysosome-related vesicles containing an electrogenic H+ATPase, a chloride channel, LAMP-1, and cathepsin K. In consequence, resorption of bone reflects secretion of HCl to mobilize mineral, and cathepsin K to degrade the collagen-rich organic matrix, into the resorptive space: Stenbeck, 2002; Zhao et al., 2008). We …