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GSBS Dissertations and Theses

2013

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Full-Text Articles in Medicine and Health Sciences

A Role For Neuronal Nicotinic Acetylcholine Receptors In Dopamine-Mediated Behaviors And The Hypnotic Response To Anesthetics: A Dissertation, Lindsey G. Soll Dec 2013

A Role For Neuronal Nicotinic Acetylcholine Receptors In Dopamine-Mediated Behaviors And The Hypnotic Response To Anesthetics: A Dissertation, Lindsey G. Soll

GSBS Dissertations and Theses

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels that most notably influence dopamine (DA) release. In this thesis, I examine the role of nAChRs in mediating DA-related behaviors such as movement and drug dependence. To accomplish this, I utilized a “gain-offunction” knock-in mouse (the Leu9’Ala line) containing agonist-hypersensitive α4* nAChRs (* indicates other nAChR subunits in addition to α4 are within the receptor complex) that renders receptors 50-fold more sensitive to nicotine and acetylcholine than wild-type (WT) receptors. I found that DHβE, a selective antagonist for α4β2* nAChRs, induced reversible and robust motor dysfunction characterized by hypolocomotion, akinesia, catalepsy ...


Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks Jun 2013

Modulating Influenza And Heparin Binding Viruses’ Pathogenesis With Extrinsic Receptor Decoy Liposomes: A Dissertation, Gabriel L. Hendricks

GSBS Dissertations and Theses

Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors ...


Dynamic Regulation At The Neuronal Plasma Membrane: Novel Endocytic Mechanisms Control Anesthetic-Activated Potassium Channels And Amphetamine-Sensitive Dopamine Transporters: A Dissertation, Luke R. Gabriel Jun 2013

Dynamic Regulation At The Neuronal Plasma Membrane: Novel Endocytic Mechanisms Control Anesthetic-Activated Potassium Channels And Amphetamine-Sensitive Dopamine Transporters: A Dissertation, Luke R. Gabriel

GSBS Dissertations and Theses

Endocytic trafficking dynamically regulates neuronal plasma membrane protein presentation and activity, and plays a central role in excitability and plasticity. Over the course of my dissertation research I investigated endocytic mechanisms regulating two neuronal membrane proteins: the anesthetic-activated potassium leak channel, KCNK3, as well as the psychostimulant-sensitive dopamine transporter (DAT). My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. Additionally, PKC-mediated KCNK3 trafficking requires a non-canonical endocytic motif, which is shared exclusively ...


Rna Interference By The Numbers: Explaining Biology Through Enzymology: A Dissertation, Liang Meng Wee Jun 2013

Rna Interference By The Numbers: Explaining Biology Through Enzymology: A Dissertation, Liang Meng Wee

GSBS Dissertations and Theses

Small silencing RNAs function in almost every aspect of cellular biology. Argonaute proteins bind small RNA and execute gene silencing. The number of Argonaute paralogs range from 5 in Drosophila melanogaster , 8 in Homo sapiens to an astounding 27 in Caenorhabditis elegans. This begs several questions: Do Argonaute proteins have different small RNA repertoires? Do Argonaute proteins behave differently? And if so, how are they functionally and mechanistically distinct?

To address these questions, we examined the thermodynamic, kinetic and functional properties of fly Argonaute1 (dAgo1), fly Argonaute2 (dAgo2) and mouse Argonaute2 (mAGO2). Our studies reveal that in fly, small RNA ...


The Study Of Two Strategies For Decreasing Mutant Huntingtin: Degradation By Puromycin Sensitive Aminopeptidase And Rna Interference: A Dissertation, Joanna Chaurette May 2013

The Study Of Two Strategies For Decreasing Mutant Huntingtin: Degradation By Puromycin Sensitive Aminopeptidase And Rna Interference: A Dissertation, Joanna Chaurette

GSBS Dissertations and Theses

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion in exon 1 of the huntingtin gene, resulting in an expanded polyglutamine (polyQ) repeat in the huntingtin protein. Patients receive symptomatic treatment for motor, emotional, and cognitive impairments; however, there is no treatment to slow the progression of the disease, with death occurring 15-20 years after diagnosis. Mutant huntingtin protein interferes with multiple cellular processes leading to cellular dysfunction and neuronal loss. Due to the complexity of mutant huntingtin toxicity, many approaches to treating each effect are being investigated. Unfortunately, addressing one cause of toxicity ...


The Effects Of Family And Social Engagement On The Screen Time Of Youth With Developmental Disabilities: A Dissertation, Charmaine B. Lo May 2013

The Effects Of Family And Social Engagement On The Screen Time Of Youth With Developmental Disabilities: A Dissertation, Charmaine B. Lo

GSBS Dissertations and Theses

Developmental disabilities (DEVDIS) such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), developmental delay (DD), and learning disabilities, affect 14% of US youth, who also experience higher rates of obesity, approximately 19%, than youth without these conditions. Screen time is a risk factor for obesity, though it is not well-studied among youth with developmental disabilities. Youth with developmental disabilities experience challenges with learning, have underdeveloped social skills, and problematic behaviors. These predispositions can often result in peer rejection. The resulting social isolation may make these youth particularly vulnerable to engaging in solitary activities such as screen time. The ...


Elucidating The Molecular Mechanism Of Cyld-Mediated Necrosis: A Dissertation, David M. Moquin May 2013

Elucidating The Molecular Mechanism Of Cyld-Mediated Necrosis: A Dissertation, David M. Moquin

GSBS Dissertations and Theses

TNFα-induced programmed necrosis is a caspase-independent cell death program that is contingent upon the formation of a multiprotein complex termed the necrosome. The association of two of the components of the necrosome, receptor interacting protein 1 (RIP1) and RIP3, is a critical and signature molecular event during necrosis. Within this complex, both RIP1 and RIP3 are phosphorylated which are consequential for transmission of the pro-necrotic signal. Namely, it has been demonstrated that RIP3 phosphorylation is required for binding to downstream substrates. Nevertheless, the regulatory mechanisms governing necrosome activation remain unclear. Since necrosis is implicated in a variety of different diseases ...


Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett Apr 2013

Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett

GSBS Dissertations and Theses

In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches.

My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of ...


Local Macrophage Proliferation In Adipose Tissue Is A Characteristic Of Obesity-Associated Inflammation: A Dissertation, Shinya U. Amano Mar 2013

Local Macrophage Proliferation In Adipose Tissue Is A Characteristic Of Obesity-Associated Inflammation: A Dissertation, Shinya U. Amano

GSBS Dissertations and Theses

Obesity and diabetes are major public health problems facing the world today. Extending our understanding of adipose tissue biology, and how it changes in obesity, will hopefully better equip our society in dealing with the obesity epidemic. Macrophages and other immune cells accumulate in the adipose tissue in obesity and secrete cytokines that can promote insulin resistance. Adipose tissue macrophages (ATMs) are thought to originate from bone marrow-derived monocytes, which infiltrate the tissue from the circulation. Much work has been done to demonstrate that inhibition of monocyte recruitment to the adipose tissue can ameliorate insulin resistance. While monocytes can enter ...


Runx Expression In Normal And Osteoarthritic Cartilage: Possible Functions Of Runx Proteins In Chondrocytes: A Dissertation, Kimberly T. Leblanc Feb 2013

Runx Expression In Normal And Osteoarthritic Cartilage: Possible Functions Of Runx Proteins In Chondrocytes: A Dissertation, Kimberly T. Leblanc

GSBS Dissertations and Theses

The Runx family of transcription factors supports cell fate determination, cell cycle regulation, global protein synthesis control, and genetic as well as epigenetic regulation of target genes. Runx1, which is essential for hematopoiesis; Runx2, which is required for osteoblast differentiation; and Runx3, which is involved in neurologic and gut development; are expressed in the growth plate during chondrocyte maturation, and in the chondrocytes of permanent cartilage structures. While Runx2 is known to control genes that contribute to chondrocyte hypertrophy, the functions of Runx1 and Runx3 during chondrogenesis and in cartilage tissue have been less well studied.

The goals of this ...