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Biology

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Western Michigan University

Dissertations

2007

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Mapk Survival Signaling In Melanoma, Matthew W. Vanbrocklin Dec 2007

Mapk Survival Signaling In Melanoma, Matthew W. Vanbrocklin

Dissertations

Extracellular signals activate mitogen-activated protein kinase (MAPK) cascades potentiating biological activities such as cell proliferation, differentiation, and survival. Constitutive activation of MAPK signaling pathways is implicated in the development and progression of many human cancers, including melanoma. Mutually exclusive activating mutations in NRAS or BRAF are found in ∼85% of all melanomas resulting in constitutive activation of the MAPK pathway (RAS-BRAF-MEK-ERK-RSK). We have previously demonstrated that inhibition of this pathway with small molecule MEK inhibitors selectively induces apoptosis in human melanoma cells both in vitro and in vivo, but not in normal melanocytes. These results support the notion that the …


The Effects Of Aging And Activity On Glial Cell Line-Derived Neurotrophic Factor Expression In Skeletal Muscle, Nathan Peplinski Aug 2007

The Effects Of Aging And Activity On Glial Cell Line-Derived Neurotrophic Factor Expression In Skeletal Muscle, Nathan Peplinski

Dissertations

Glial cell line-derived neurotrophic factor (GDNF) is an extracellular signaling protein that is produced by skeletal muscle and is important for the motor neurons that control muscle movement. GDNF has been shown to keep neurons alive under conditions that they would otherwise not persist. In skeletal muscle, GDNF has been shown to be one of the most potent neurotrophic factors that influence motor neuron survival. While the role of GDNF has been well studied during early development, not much is known about what happens to GDNF expression in the adult and with advanced aging. Previous results from our lab have …


Structure-Function Studies Of Self- Assembling Flagellin Proteins Fromsalmonella Typhimurium And Aquifex Pyrophilus, Venkata Raghu Ram Malapaka Jun 2007

Structure-Function Studies Of Self- Assembling Flagellin Proteins Fromsalmonella Typhimurium And Aquifex Pyrophilus, Venkata Raghu Ram Malapaka

Dissertations

The eubacterial flagellum is a complex structure with an elongated extracellular filament that is primarily composed of a single protein termed flagellin. The highly conserved N-and C- termini of flagellin are important in its export and assembly, whereas the middle "hypervariable" region is highly variable in size across different species and is largely dispensable. InSalmonella typhimurium phase 1 flagellin (FliC), this hypervariable region encodes two solvent-exposed D2 and D3 domains. The functional role of this knob-like structural feature in motility remains unclear. The structural and physiological role of the hypervariable region in flagellar assembly, stability and cellular motility was investigated. …