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The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter Jan 2014

The Role Of Wnt5a In Tumor Suppression And Differentiation, Stephanie Easter

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TGF-beta and the Wnt signaling pathways play key roles in regulating ductal growth and branching morphogenesis in the mammary gland. Disruption to this signaling can cause deregulation of the normal mammary stem cell population and foster an environment favorable for tumorigenesis and recurrence. Recent studies show that TGF-beta up-regulates expression of the non-canonical Wnt, Wnt5a, in the mammary gland and that Wnt5a antagonizes canonical Wnt/beta-catenin signaling in mammary epithelial cells. Canonical Wnt/beta-catenin signaling has been strongly implicated in expanding the mammary stem/progenitor cell pool. Here, we test the hypothesis that Wnt5a suppresses the expansion of the mammary stem and progenitor …

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Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley Jan 2014

Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley

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Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors combine to influence an individual's predilection for breast cancer and related metastatic tumor formation. The genetic component, in particular, has become the focus of many emergent studies. A renewed focus on cancer metabolism and the Warburg effect has similarly cast a spotlight on the role, if any, of the mitochondrion in directing disease progression. Analysis of the direct contribution of mitochondrial DNA on tumorigenicity is made possible through the use of mitochondrial-nuclear exchange (MNX) mice in which nuclei from normal FVB mice (the background strain of the tg: …

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Exploring Novel System Biology Approaches To Understand The Molecular Mechanisms Of Immune Responses, Cassandra Camille Garbutt Jan 2014

Exploring Novel System Biology Approaches To Understand The Molecular Mechanisms Of Immune Responses, Cassandra Camille Garbutt

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nesting behavior on sex ratios and survival of eggs and hatchlings. The results indicate

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Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano Jan 2014

Mitochondrial Dysfunction In Response To Neurotoxins And The Role Of Mitophagy, Samantha Giordano

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Parkinson's disease (PD) is the second most common neurodegenerative disorder. Two major factors in both familial and sporadic PD are mitochondrial dysfunction and insufficient autophagy. My thesis research focuses on the interplay between these activities in PD. To investigate the common and differential effects of PD-inducing neurotoxins on mitochondrial bioenergetics and their relationships to cell survival, we used an in vitro culture system, differentiated dopaminergic SH-SY5Y neuroblastoma cells. We found that the neurotoxins rotenone, 1-methyl-4- phenylyridinium (MPP+) and 6-hydroxydopamine (6-OHDA), decreased mitochondrial respiration and induced cell death in these cells. The extent and characteristics of mitochondrial dysfunction in response to …

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Therapeutic Ck2 Inhibition Attenuates Diverse Prosurvival Signaling Cascades And Decreases Cell Viability In Human Breast Cancer Cells, Gary Kenneth Gray Jan 2014

Therapeutic Ck2 Inhibition Attenuates Diverse Prosurvival Signaling Cascades And Decreases Cell Viability In Human Breast Cancer Cells, Gary Kenneth Gray

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Breast cancer is the most common malignancy in women worldwide, and it remains a major cause of mortality, thus necessitating further advancements in treatment. In breast cancer, numerous cell signaling pathways are aberrantly activated in order to produce the myriad phenotypes associated with malignancy; such pathways include the PI3K/Akt/mTOR, NF-κB and JAK/STAT cascades. These pathways are highly interconnected, but one prominent lateral enhancer of each is the remarkably promiscuous kinase CK2. CK2 expression has been shown to be elevated in human cancer, thus implicating it in tumorigenesis through its effects on known oncogenic signaling cascades. In this study, differential aberrant …

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Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic Jan 2014

Regulation Of Skeletal Muscle Plasticity Using Engineered Configurations Of The Transcription Factors Myod And E12, Vladimir Grubisic

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Skeletal muscle fibers, although terminally differentiated, can change their features, such as contraction speed and endurance, and throughout adult life in response to variety of stimuli, like exercise. This process is called plasticity and is mainly regulated by the type of nerve activity. Over the past several decades, research has shown that the properties of myofibers are also determined during muscle development. Ultimately, the change in phenotype requires a change in gene expression which is, in turn, regulated by transcription factors (TFs). Basic helix-loop-helix (bHLH) TFs regulate myogenesis and the central role belongs to the myogenic differentiation 1 (MyoD), often …

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The Role Of Human Ficolin-2 During Invasive Pneumococcal Disease, Allison Marie Brady Jan 2014

The Role Of Human Ficolin-2 During Invasive Pneumococcal Disease, Allison Marie Brady

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Streptococcus pneumoniae (pneumococcus) is a significant human pathogen that typically resides in the nasopharynx of humans. The major virulence factor of pneumococcus is its capsular polysaccharide, of which it can express over 90 unique serotypes. However, there is great disparity in which serotypes colonize or cause disease, though the reason for these differences are not well understood. Serotype 11A is one such serotype that frequently colonizes the nasopharynx of children, but rarely causes disease. Interestingly, serotype 11E, a variant of 11A, varies only in the O-acetylation of a galactose residue in its polysaccharide repeating unit. This difference in structure is …

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Determining The Role Of Neuregulin-1 And Its Erbb Receptors In The Pathogenesis Of Malignant Peripheral Nerve Sheath Tumors, Stephanie Brosius Jan 2014

Determining The Role Of Neuregulin-1 And Its Erbb Receptors In The Pathogenesis Of Malignant Peripheral Nerve Sheath Tumors, Stephanie Brosius

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Malignant peripheral nerve sheath tumors (MPNSTs) are the most common cause of death in patients with neurofibromatosis type-1. These aggressive, Schwann cell-derived tumors have no treatment beyond surgical resection. Developing targeted chemotherapeutics remains crucial to improving patient survival. The Schwann cell mitogen neuregulin-1 (NRG1) was shown to mediate the migration, proliferation and survival of MPNSTs. Furthermore, overexpression of NRG1 in Schwann cells (P0-GGF beta 3 mice) on an outbred C57BL/6J x SJL/J background induced the formation of neurofibromas and MPNSTs similar to human disease, yet these mice have intact neurofibromin. To determine if NRG1 acts within the same signaling cascade …

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Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman Jan 2014

Cd5-Dependent Ck2 Activation Is Critical For The Maintenance Of B-1a B Cells, Kevin S. Cashman

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CD5 has classically been shown to act as a negative regulator of antigen receptor signaling, however recent evidence has discerned that the CD5 molecule contains a previously undefined cytoplasmic domain which constitutively binds inactive CK2 and facilitates its activation through CD5 ligation. With the development of a mouse model which contains a micro-deletion knock-in form of CD5 which lacks the amino acids necessary to facilitate this CD5-CK2 interaction, it is now understood that CD5 plays a more significant role in cellular physiology than previously appreciated. T cells from this mouse model show increased AICD and dysregulation in T helper subset …

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The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black Jan 2014

The Modulation Of High Density Lipoprotein Metabolism In Systemic Lupus Erythematosus, Leland Latham Black

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Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can suppress inflammation and autoimmunity in hypercholesterolemic mice by modulating cellular cholesterol homeostasis and lipid oxidation. However, the cellular and molecular mechanisms involved are poorly understood, and whether ApoA-I or ApoA-I mimetic peptides can similarly exert immunosuppressive effects or improve inflammatory organ disease in SLE under normolipidemic conditions remains unresolved. We therefore first took a genetic approach in which bone marrow from SLE-prone Sle123 mice was transferred into wild-type, ApoA-I knockout (ApoA-I-/-) and ApoA-I transgenic (ApoA-Itg) mice. Transgenic expression of ApoA-I suppressed CD4+ T and B lymphocyte activation, reduced …

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The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser Jan 2014

The Role Of The Developing Microbiome In Mucosal Defense Of The Neonatal Gut, Emily G. Blosser

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Neonatal late-onset sepsis is invasive infection occurring after the first 48 hours of life, and one of the leading causes of death among preterm infants in the United States and abroad. Infections with Gram-negative bacteria, such as Klebsiella pneumonia, occurring when bacteria translocate across premature gut epithelium into the bloodstream, can be particularly severe. Preterm infants in the neonatal intensive care unit undergo intense antibiotic regimens due to high risk of infection. Paradoxically, prolonged exposure of preterm infants to empiric antibiotic therapy early in the hospital stay is associated with increased risk of intestinal infection and death after adjustment for …

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Exposure To Methylmercury Via Fish Consumption In Ghana And An Evaluation Of Methylmercury Toxicity Under A Low Food Ration In Daphnia Pulex, Dzigbodi Adzo Doke Jan 2014

Exposure To Methylmercury Via Fish Consumption In Ghana And An Evaluation Of Methylmercury Toxicity Under A Low Food Ration In Daphnia Pulex, Dzigbodi Adzo Doke

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For many people of the world, fish is a primary source of protein, especially in countries like Ghana, where about 60% of the protein consumed is derived from fish. Fish advisories have been established by some nations to protect the public from harmful health effects linked to eating contaminated fish. Methylmercury (MeHg) is one such contaminant that has resulted in fish advisories. Fish advisories have not been developed in Ghana, although MeHg contamination of aquatic ecosystems is likely due to the long history of mercury (Hg) use in artisanal gold mining. To address this gap in our knowledge, I compiled …

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Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin Jan 2014

Development Of A Patient-Derived Xenograft Model Of Ovarian Cancer To Characterize The Chemotherapy Resistant Population, Zachary Christopher Dobbin

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Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian …

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The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha Jan 2014

The Role Of The Planar Cell Polarity Pathway In The Second Heart Field During Outflow Tract Morphogenesis, Tanvi Sinha

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Outflow Tract (OFT) malformations underlie a majority of congenital heart defects (CHD) in humans and are a leading cause of childhood mortality. The OFT, which gives rise to the aorta and pulmonary artery of the heart, relies on the contribution of the Second Heart Field (SHF) progenitors in the pharyngeal and the splanchnic mesoderm, outside of the initial heart. OFT morphogenesis requires highly regulated SHF development involving the proliferation, differentiation and deployment of the SHF progenitors to the heart. Extensive studies elegantly demonstrate how transcriptional networks integrating signaling input from multiple pathways finely balance the proliferation and differentiation of SHF …

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Neuroplastic Change In Adults With Hemiparetic Multiple Sclerosis Following Constraint-Induced Movement Therapy, Chelsey Sterling Jan 2014

Neuroplastic Change In Adults With Hemiparetic Multiple Sclerosis Following Constraint-Induced Movement Therapy, Chelsey Sterling

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Constraint-Induced Movement (CI) therapy has been found to produce substantial improvements in upper-extremity functioning in both adults and children following damage to the central nervous system (CNS), including stroke, traumatic brain injury and cerebral palsy. In addition, structural changes in the sensorimotor cortices and bilateral hippocampi have been observed in both adults and children following CI therapy treatment for upper extremity hemiparesis. Although most research has been conducted in patients with such static injuries as strokes and TBI, clinical efficacy of CI therapy has also been demonstrated in a small number of patients with the progressive autoimmune disorder, multiple sclerosis …

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Studying The Looping Cycle In Early Childhood Public Education: A Multiple Case Study Analysis, Katherine Allsopp Thomas Jan 2014

Studying The Looping Cycle In Early Childhood Public Education: A Multiple Case Study Analysis, Katherine Allsopp Thomas

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STUDYING THE LOOPING CYCLE IN EARLY CHILDHOOD PUBLIC EDUCATION: A MULTIPLE CASE STUDY ANALYSIS KATHERINE ALLSOPP THOMAS CURRICULUM AND INSTRUCTION, EARLY CHILDHOOD EDUCATION ABSTRACT This study addressed the nature of the looping cycle in early childhood public education in central Alabama. In addition, factors were explored that influence a teacher's decision to loop as well as the reasons behind why the practice is not more prevalent in early childhood public education. The purpose of this research was to describe the nature of the looping cycle for early childhood public education teachers in central Alabama in order to understand why looping …

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Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell Jan 2014

Characterization Of Phosphatidylinositol 4,5-Bisphosphate Regulation Of The Electrogenic Na/Bicarbonate Cotransporter Nbce1, Ian Michael Thornell

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The electrogenic Na/bicarbonate cotransporter (NBCe1) is an acid/base regulator that is also involved in coordinating epithelial ion transport. Splice variants of NBCe1 differ at their cytosolic amino- (N-) and/or carboxy- (C-) termini. These different cytosolic termini impart differential regulation for each variant. For example, the N-terminus of NBCe1-A is autostimulatory, whereas the N-terminus of NBCe1-B and -C is autoinhibitory. We examine the regulatory role of PIP2 for NBCe1 splice variants. In the first study of this dissertation, we characterize the effect of increasing PIP2 on the activity of NBCe1-A, -B, and -C expressed in Xenopus laevis oocytes. Injecting PIP2 stimulated …

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Peripheral Neuropathy In The Teetering Mice Results From Mutation Of The Escrt Component Hrs, Jennifer Ashley Watson Jan 2014

Peripheral Neuropathy In The Teetering Mice Results From Mutation Of The Escrt Component Hrs, Jennifer Ashley Watson

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The sorting and degradation of endocytosed cargo by the endosome regulates many cellular functions common to all cells. Neural cells appear to be particularly vulnerable to perturbation in endo-lysosomal transport, and several neurological disorders are caused by a primary deficit in this pathway. In this dissertation, I show that the spontaneously occurring neurological mutation teetering (tn) is a single nucleotide substitution in the endosomal cargo-sorting component hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs) that reduces the abundance of HRS. By 3 weeks of age, the tn mice exhibit heightened pain sensitivity, muscle weakness and reduced muscle size. The loss of …

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Development Of A High-Throughput Self-Interaction Chromatography System, David Johnson Jan 2014

Development Of A High-Throughput Self-Interaction Chromatography System, David Johnson

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The first recombinant human protein drug, insulin expressed in e.coli cells, was approved by the FDA in 1982. Since then, protein therapeutics have become the fastest growing segment of the pharmaceutical industry and include immunoglobulin-g (IgG) directed cancer and immune disorder treatments. A major difficulty to bring protein drugs to market is the requirement that they be concentrated up to 150 mg/ml without aggregation for efficacy in a small injection volume. One way to improve protein drug solubility is to include additives that reduce protein-protein attraction and increase protein-protein repulsion thereby preventing protein molecules from coming together to form aggregates. …

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Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza Jan 2014

Mechanisms Of At101 [(-)-Gossypol] Induced Cytotoxicity In Malignant Peripheral Nerve Sheath Tumors, Niroop Kaza

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Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and are the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective resulting in a high rate of MPNST recurrence and poor five year patient survival. This necessitates the exploration of alternative chemotherapeutic options for MPNST patients. By evading apoptosis and utilizing protective mechanisms such as autophagy, cancer cells develop resistance to chemo- and radio-therapy. The overall goal of my thesis studies is to evaluate chemotherapeutic agents that can modulate both apoptosis and autophagy, thus target both cell death pathways …

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Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar Jan 2014

Development Of An Axonal Outgrowth Assessment Methodology For Dorsal Root Ganglia Explants And Demonstration Of Method Efficacy On Electrospun Polymer Scaffolds, Sarah Margaret Kezar

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In chronic spinal cord injury (SCI), a glial encapsulated cyst develops at the injury site and acts as a physical and biochemical barrier to regeneration. Discussion has suggested that filling the cyst with a growth promoting scaffold is a promising approach to cure chronic SCI, though the research to date lacks a systematic approach. Dorsal root ganglia (DRG) explants are an extremely common tissue culture model of neural regeneration employed in this field, however there is no uniform method for objectively quantifying substrate biocompatibility and neurite outgrowth. Therefore, we aimed to develop a novel DRG growth assessment methodology and to …

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The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg Jan 2014

The Direct Effects And Vertical Transfer Of Carbonaceous And Metal-Loaded Hydrochars In Aquatic Organisms, Katie Lauren Kohlenberg

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Industrial use of reactive micro- and nano-sized carbonaceous hydrochar (CH) is expanding rapidly. These carbonaceous particulates are synthesized by the pyrolysis of biomass in an industrial process called hydrothermal carbonization (HTC) and have gained attention as a soil conditioner. Additionally, the HTC process is being expanded to coat heavy-metal nanoparticles, such as nano-copper and nano-iron, to prevent surface oxidation of these metals. These carbonaceous particles are likely to undergo secondary reactions with metals, toxicants, or other compounds. There is potential for these carbonaceous particulates to enter watersheds and have deleterious effects on aquatic food web dynamics. In this study, we …

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Effect Of Abutment Position On Retention After Cyclic Loading Of Cantilevered Y-Tzp Fpds, Aikaterini Kostagianni Jan 2014

Effect Of Abutment Position On Retention After Cyclic Loading Of Cantilevered Y-Tzp Fpds, Aikaterini Kostagianni

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Purpose: The influence of the vertical abutment positions on the retention of a three-unit implant supported cantilevered FPD restoration was measured and compared. Methods: The study included four groups (n=10) of cantilevered FPDs restorations, fabricated of monolithic zirconia. Prefabricated titanium implant abutments were used and connected to their analogs. The analogs were fixated on a split mold and their vertical position was adjusted on a 2 mm bases depending on the group, resulting also to an alteration of the occlusal thickness of the restorative material. The prosthesis were cemented to the abutments with Rely X Luting Plus resin modified glass …

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Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li Jan 2014

Evaluation Of Tau As A Target For Alzheimer Disease And Other Conditions With Epileptiform Activity, Zhiyong Li

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Alzheimer disease (AD) is a devastating neurological condition that slowly destroys memory and thinking skills of the affected patients. No disease-modifying medications are available. While all the treatment against Aߒ (major component of one hallmark pathology of AD) failed in clinical trials, tau (major component of the other hallmark pathology of AD) is emerging as a better alternative. Germline knockout of tau does not cause overt abnormalities in young mice and prevents AD-like deficits in mouse models of AD. Germline knockout of tau also confers resistance to epileptiform activity in models of both AD and epilepsy. Therefore tau is proposed …

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Poly(N-Vinylcaprolactam) Based Thermoresponsive Nanostructured Materials, Xing Liang Jan 2014

Poly(N-Vinylcaprolactam) Based Thermoresponsive Nanostructured Materials, Xing Liang

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Poly(N-vinylcaprolactam) (PVCL) is a temperature-responsive polymer displaying a low critical solution temperature (LCST) around 30 to 40℃ in aqueous solutions that is close to the human physiological temperature. In addition, compared to other ther-moresponsive polymers, PVCL is nontoxic and biocompatible. In this thesis, we will fo-cus on the synthesis, fabrication and characterization of PVCL-based thermoresponsive nanostructured materials, such as films, hydrogels and block copolymers and their poten-tial applications in biomedical and medical areas. In chapter 2, we report on nanothin multilayer hydrogels of cross-linked PVCL that exhibited distinctive and reversible thermoresponsive behavior. The single-component PVCL hydrogels were produced by selective …

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Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero Jan 2014

Anatomical And Neurochemical Investigation Of The Brain In Autism, Lauren E. Libero

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with widespread behavioral symptoms and a strong neurobiological origin. Neuroimaging studies of ASD have uncovered evidence for widespread abnormalities in brain anatomy and functioning. Abnormalities reported by structural brain imaging, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) studies have aided in characterizing ASD as a complex, systems-wide disorder. The overarching goal of this project was to use multiple modalities of neuroimaging to investigate the underlying neural mechanisms of ASD. The following techniques were used to collect and analyze multimodal neuroimaging data from a relatively large number of participants …

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Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin Jan 2014

Ksrp Ablation Enhances Lipolysis In White Adipose Tissue Through Reduced Mir-145 Expression, Yi-Yu Lin

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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol (TAG) for energy source. Here, we report that null mice for KH-type splicing regulatory protein (KSRP), an RNA-binding protein, resisted high fat diet (HFD) induced obesity. Target of deletion of KSRP regulates gene expression at multiple levels and enhances lipolysis in epididymal WAT (eWAT) due to up-regulation of genes promoting lipolytic activity. Expression of miR-145 is decreased due to impaired pri-miR-145 processing in Ksrp-/- eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals …

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Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker Jan 2014

Transmitted/Founder Siv In The Rhesus Macaque Model Of Hiv-1 Infection, Mike Lopker

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Vitally important to HIV-1 vaccine and prevention studies is a well-characterized animal model that recapitulates the salient features of HIV infection in humans. SIVmac and SIVsmm infection of rhesus macaques share key virological and pathological parallels with HIV-1 infection of humans including target cell entry via CD4 and CCR5 (Edinger et al., 1997), progressive T cell loss (Swanstrom & Coffin, 2012), generalized immune activation and preferential loss of mucosal Th17 cells (Brenchley et al., 2008; Klatt & Brenchley, 2010), and a vigorous but ultimately ineffective adaptive immune response. Though commonly used as a vaccine challenge strain in the macaque model, …

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Exploring Intrinsic Biomarkers For Optical Assessment Of Outer Retina, Rongwen Lu Jan 2014

Exploring Intrinsic Biomarkers For Optical Assessment Of Outer Retina, Rongwen Lu

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The retina suffers pathological changes after attacked by eye diseases. The objective of my PhD dissertation is to explore intrinsic biomarkers for noninvasive assessment of retinal morphological structure and physiological function. Fundus autofluorescence (FAF), optical coherence tomography (OCT), etc. have provided indispensable information for eye disease detection. However, better understanding of the intrinsic biomarkers in FAF and OCT is desirable for quantitative interpretation of clinical outcomes. The first specific aim of the dissertation research was to characterize FAF signals across the whole retinal depth using two-photon excitation. FAF signals are usually attributable to fluorophores from the choroidal vessel and the …

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The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader Jan 2014

The Role Of The Autophagy-Lysosome Pathway In In Vitro Models Of Neurodegeneration, Burton Mader

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Recent studies have provided strong evidence that alterations in protein degradation pathways, such as the autophagy-lysosome pathway (ALP), may contribute to neuronal dysfunction and death which lead to clinical symptoms diagnosed with various neurodegenerative diseases. Parkinson's disease (PD) is characterized by neuromuscular abnormalities resulting from the pathological loss of substantia nigra dopaminergic neurons and widespread detection of Lewy bodies, intracellular protein inclusions composed primarily of α-synuclein. Additionally, altered gene function regulating the expression of α-synuclein has been directly linked to the PD pathogenesis. Autophagy is an intracellular degradation process that when altered can lead to the accumulation neurotoxic proteins such …

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