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Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
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ABSTRACT OF THE DISSERTATION Isoform-specific roles of Extracellular Signal-Regulated Kinases in pain by Benedict Joseph Alter Doctor of Philosophy in Biology and Biomedical Sciences Neurosciences Washington University in St. Louis, 2012 Professor Robert Gereau, Chairperson The extracellular signal-regulated kinase: ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies utilizing inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase: MEK), and transgenic mice expressing a dominant negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the …
The Role Of The Intestinal Microbiota In Inflammatory Bowel Disease, Seth Bloom
The Role Of The Intestinal Microbiota In Inflammatory Bowel Disease, Seth Bloom
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Inflammatory bowel disease: IBD) arises from complex interactions of genetic, environmental, and microbial factors. The intestinal microbiota is crucial for IBD induction and complex shifts in microbiota composition occur in IBD, but disease has not been consistently associated with presence or absence of a specific microbe. It is thus controversial whether fulfilling Koch's postulates for individual bacterial species is relevant to IBD and whether disease-associated alterations in microbial colonization are predictive of underlying etiology. Resolving these controversies has been challenging due to paucity of animal models with rapid disease onset, experimental reliance on gnotobiotic animals, and difficulty specifically isolating many …
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
The Role Of Autophagy And Il-17 In Bone Resorption, Carl Deselm
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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 …
Allosteric Modulation Of Metabotropic Glutamate Receptor 5 As A Treatment For Pain, Michael Montana
Allosteric Modulation Of Metabotropic Glutamate Receptor 5 As A Treatment For Pain, Michael Montana
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Metabotropic glutamate receptor 5: mGlu5) has been suggested to play a role in the development and maintenance of chronic pain. mGlu5 is expressed at synapses throughout the pain neuraxis where it is believed to modulate the function of ion channels that underlie nociceptive transduction and transmission. Injections of mGlu5 agonists cause hypersensitivity or nocifensive behavior when administered peripherally, intrathecally, and centrally. In addition, pharmacological antagonism of mGlu5 has been suggested to be analgesic in a variety of animal pain models. Unfortunately, the selectivity of antagonists used in these studies has been called into question, suggesting that at least some of …