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Full-Text Articles in Molecular Biology

Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers Jan 2018

Impact Of Acute Heat Treatment On Autophagy And Insulin Signaling In C2c12 Myotubes, Corey Michael Summers

Graduate Theses and Dissertations

A major risk factor for the development of type 2 diabetes is reduced skeletal muscle insulin sensitivity. It is known that exercise and caloric restriction can improve skeletal muscle insulin resistance, but the mechanism by which this occurs is not completely elucidated. The AMP-activated protein kinase (AMPK), is thought to be a major contributor to the metabolic benefits observed after exercise training and caloric restriction. Activation of AMPK in skeletal muscle can have a wide range of effects, one of which is the initiation of macroautophagy (herein referred to as autophagy). Autophagy is the bulk degradation system of the cell ...


Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers Mar 2017

Mass-Spectrometry Based Proteomics Of Age-Related Changes In Murine Microglia, Antwoine Flowers

Graduate Theses and Dissertations

The last century has seen a steady increase in the extension of the average lifespan. This has concomitantly produced higher incidences of age-related chronic degenerative diseases like Alzheimer’s and Parkinson’s diseases. Age is the single greatest risk factor for the development of not just these degenerative conditions but cancer as well. The aged niche undergoes a number of maladaptive changes that allow underlying conditions to present and progress. Exactly which changes, contribute to the progression of which disease is currently an area of intense study. However, these answers often present therapeutic targets for disease prevention. Age is characterized ...


Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert Jun 2016

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of ...


Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic Jan 2015

Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction ...


Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco Jan 2015

Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco

Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS ...


Design And Evaluation Of Immunogens Based On Gp41 Membrane-Proximal External Region For Development Of A Vaccine Against Human Immunodeficiency Virus Type 1, Saikat Banerjee Jan 2015

Design And Evaluation Of Immunogens Based On Gp41 Membrane-Proximal External Region For Development Of A Vaccine Against Human Immunodeficiency Virus Type 1, Saikat Banerjee

Graduate Theses and Dissertations

Since its discovery in 1981, HIV-1 has infected ~78 million people and killed ~39 million people. Developing an HIV-1 vaccine remains one of the top priorities in the fight against this devastating pandemic. The modest efficacy showed by the recent RV144 trial suggests that achieving this goal might be possible. As the search for an effective vaccine continues, the induction of antibodies that can neutralize a large number of antigenically distinct viruses from different clades remains a major goal. In recent years, a number of broadly neutralizing antibodies (bnAbs) that target the HIV-1 envelope have been isolated from virus-infected patients ...


Molecular Characterization Of Human, Bovine, And Dolphin Parainfluenza Viruses: Viral Genome Sequencing And Epithelial Cell Signaling Responses Following In Vitro Infection, Kirsten Charlotte Eberle Jan 2015

Molecular Characterization Of Human, Bovine, And Dolphin Parainfluenza Viruses: Viral Genome Sequencing And Epithelial Cell Signaling Responses Following In Vitro Infection, Kirsten Charlotte Eberle

Graduate Theses and Dissertations

This dissertation aims at examining immunological response(s) to PIV-3 infection using in vitro cell culture systems. Based on previous publications, TtPIV-1 was found to be similar to, but distinct from, both human and bovine PIV-3 isolates. These initial findings were based only upon partial sequences of the F and HN viral genes. In Chapter 2 TtPIV-1 is further characterized on cytokine production, viral growth over time, and full genome sequencing as compared to BPIV-3 and HPIV-3. Chapter 3 is aimed at examining the type III IFN response during TtPIV-1, BPIV-3, and HPIV-3 infection. Because paramyxoviruses are known to affect ...


Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova May 2014

Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova

Graduate Theses and Dissertations

Angelman Syndrome (AS) is a severe neurodevelopmental disorder that affects 1:12000 newborns. It is characterized by mental retardation, delayed major motor and cognitive milestones, seizures, absence of speech and excessive laughter. The majority of AS cases arise from deletions or mutations of UBE3A gene located on the chromosome 15q11-13. UBE3A codes for E3-ubiquitin ligase that target specific proteins for degradation. To date, a wide variety of Ube3a substrates has been identified. The accumulation of Ube3a-dependent proteins and their effect on the multitude of signal transduction pathways are` considered the main cause of the AS pathology. While the majority of ...


Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli Jan 2013

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the ...


Multivariate Anti-Inflammatory Approaches To Rescue Neurogenesis And Cognitive Function In Aged Animals, Sandra Antonieta Acosta Jan 2011

Multivariate Anti-Inflammatory Approaches To Rescue Neurogenesis And Cognitive Function In Aged Animals, Sandra Antonieta Acosta

Graduate Theses and Dissertations

Studies have shown that there is a strong correlation between aging and neurodegenerative diseases. Aging is considered the number one risk factor to develop neuropathologies such as memory loss, senile dementia, Alzheimer's disease (AD), and Parkinson's disease. Neurodegenerative diseases tend to start during adulthood, and aggravate over time, making them difficult to prevent and to treat. In the Unites States, demographic studies by U.S. Bureau of the Census have determined that our aging population of >65 years is expected to increase from the present 35 million to 78 million in 2030. This would result, not only to ...