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Transcriptional Regulation Of Profilin Is Required For Drosophila Larval Wound Closure, Amanda Brock

Dissertations and Theses (Open Access)

Injury is an inevitable part of life, making wound healing essential for survival. In postembryonic skin, wound closure requires that epidermal cells recognize the presence of a gap and change their behavior to migrate across it. In Drosophila larvae, wound closure requires two signaling pathways (the Jun N-terminal kinase (JNK) pathway and the Pvr receptor tyrosine kinase signaling pathway) and regulation of the actin cytoskeleton. In this and other systems, it remains unclear how the signaling pathways that initiate wound closure connect to the actin regulators that help execute wound- induced cell migrations. Here we show that chickadee, which encodes …

Platelets And Anti-Angiogenic Resistance In Ovarian Carcinoma, Justin N. Bottsford-Miller

Dissertations and Theses (Open Access)

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified.

Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of …

Regulation Of To Xin Synthesis By Clostridium Difficile, Charles Darkoh

Dissertations and Theses (Open Access)

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …

Effects Of The Acta2 R258c Mutation On Vascular Smooth Muscle Cell Phenotype And Properties, Katerina L. Byanova

Dissertations and Theses (Open Access)

Thoracic Aortic Aneurysms and Dissections (TAAD) are the fifteenth leading cause of death in the United States. About 15% of TAAD patients have family history of the disease. The most commonly mutated gene in these families is ACTA2, encoding smooth muscle-specific α-actin. ACTA2 missense mutations predispose individuals both to TAAD and to vascular occlusive disease of small, muscular arteries.

Mice carrying an Acta2 R258C mutant transgene with a wildtype Acta2 promoter were generated and bred with Acta2^-/- mice to decrease the wildtype: mutant Acta2 ratio. Acta2^{+/+ R258C TG}mice have decreased aortic contractility without aortic disease. Acta2 …

Identification And Analysis Of A Novel Role For The To Usled-Like Kinase In Regulating Mitotic Spindle Dynamics, Jason R. Ford

Dissertations and Theses (Open Access)

Deregulation of kinase activity is one example of how cells become cancerous by evading evolutionary constraints. The Tousled kinase (Tsl) was initially identified in Arabidopsis thaliana as a developmentally important kinase. There are two mammalian orthologues of Tsl and one orthologue in C. elegans, TLK-1, which is essential for embryonic viability and germ cell development. Depletion of TLK-1 leads to embryonic arrest large, distended nuclei, and ultimately embryonic lethality. Prior to terminal arrest, TLK-1-depleted embryos undergo aberrant mitoses characterized by poor metaphase chromosome alignment, delayed mitotic progression, lagging chromosomes, and supernumerary centrosomes.

I discovered an unanticipated requirement for TLK-1 …

Direct Effects Of Metformin On Pi3k And Ras Signaling In Endometrial Cancer, David A. Iglesias M.D.

Dissertations and Theses (Open Access)

Metformin has antiproliferative effects through the activation of AMPK and has gained interest as an antineoplastic agent in several cancer types, although studies in endometrial cancer (EC) are limited. The aims of this project were to evaluate pathways targeted by metformin in EC, investigate mechanisms by which metformin exerts its antiproliferative effects, and explore rational combination therapies with other targeted agents.

Three EC cell lines were used to evaluate metformin’s effect on cell proliferation, PI3K and Ras-MAPK signaling, and apoptosis. A xenograft mouse model was also used to evaluate the effects of metformin treatment on in vivo tumor growth. These …

Deciphering The C-Type Lectin Receptor Signaling Pathway In Macrophages In Response To Candida Albicans, Sara Gorjestani

Dissertations and Theses (Open Access)

Candida albicans causes opportunistic fungal infections in humans and is a significant cause of mortality and morbidity in immune-compromised individuals. Dectin-2, a C-type lectin receptor, is required for recognition of C. albicans by innate immune cells and is required for initiation of the anti-fungal immune response. We set out to identify components of the intracellular signaling cascade downstream of Dectin-2 activation in macrophages and to understand their importance in mediating the immune response to C. albicans in vivo. Using macrophages derived from Phospholipase-C-gamma 1 and 2 (PLCγ1and PLCγ2) knockout mice, we demonstrate that PLCγ2, but not PLCγ1, is required …

Ikkalpha Mediated Notch1 Activation Promotes Tumorigenesis Via Foxa2 Suppression, Mo Liu

Dissertations and Theses (Open Access)

Proinflammatory cytokine TNFa plays critical roles in promoting malignant cell proliferation, angiogenesis, and tumor metastasis in many cancers. However, the mechanism of TNFa-mediated tumor development remains unclear. Here, we show that IKKa, an important downstream kinase of TNFa, interacts with and phosphorylates FOXA2 at S107/S111, thereby suppressing FOXA2 transactivation activity and leading to decreased NUMB expression, and further activates the downstream NOTCH pathway and promotes cell proliferation and tumorigenesis. Moreover, we found that levels of IKKa, pFOXA2 (S107/ 111), and activated NOTCH1 were significantly higher in hepatocellular carcinoma tumors than in normal liver tissues and that pFOXA2 (S107/111) expression was …

Refining The Global Spatial Limits Of Dengue Virus Transmission By Evidence-Based Consensus, Oliver J. Brady, Peter W. Gething, Samir Bhatt, Jane P. Messina, John S. Brownstein, Anne G. Hoen

Dartmouth Scholarship

Background: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status.

Methods/Principle Findings: …

Charaterization And Locating Pcb-Contaminated Groundwater Entering A Stream Overlying Faulted And Folded Crystalline Rock, David Hahn

All Theses

Substantial research focused on Lake Hartwell and a major tributary, Twelvemile Creek, has provided information regarding surface transport, deposition, and biological interactions of PCBs. However, little is understood about the transport of PCBs in groundwater between the contamination site (Sangamo Weston Superfund Site in Pickens, SC) and Town Creek, a tributary to Twelvemile Creek located less than 500 m south of the contamination site. The objectives of this thesis were to 1) locate and measure groundwater influx to Town Creek, 2) determine the concentrations of PCBs in groundwater, 3) identify the colloids present in groundwater and surface water, 4) determine …

The Role Of Family Resources In The Determination Of Child Outcomes, Tengzhen Wang

All Theses

This thesis studies the role of family resources in the determination of child outcomes, specifically the degree to which family resources affect the child's years of schooling and future income. By analyzing data from the NELS (National Educational Longitudinal Study), it is found that children from families with greater financial resources typically attend school longer and earn more money than children from families with less financial resources. Child personal ability is also found to affect schooling and personal earnings.

Enzyme Actuated Bioresponsive Hydrogels, Andrew Wilson

All Theses

Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors and regenerative medicine. Conferred with the ability to respond to specific biologically derived stimuli, the design challenge is in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range and limit of detection. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide the sensing, transduction, and the actuation response of hydrogels. To investigate the dynamics of these materials, …

Continuum Limbed Robots For Locomotion, Alper Mutlu

All Theses

This thesis focuses on continuum robots based on pneumatic muscle technology. We introduce a novel approach to use these muscles as limbs of lightweight legged robots. The flexibility of the continuum legs of these robots offers the potential to perform some duties that are not possible with classical rigid-link robots. Potential applications are as space robots in low gravity, and as cave explorer robots.
The thesis covers the fabrication process of continuum pneumatic muscles and limbs. It also provides some new experimental data on this technology. Afterwards, the designs of two different novel continuum robots - one tripod, one quadruped …

Development And Characterization Of Shellac-Hydroxypropyl Methyl Cellulose Composite Films With Acid Catalyst, Sana Asrar

All Theses

The objective of this research was to develop a shellac-hydroproyl methyl cellulose (Sh-HPMC) composite film with enhanced water vapor barrier. Citric acid (CA) was used as an acid catalyst, to promote miscibility between HPMC and shellac. In a preliminary test, three different concentrations of CA (1000:1, 200:1, 100:1) were tested to identify the best Sh:CA ratio. Based on the Water vapor permeability properties and mechanical properties, Sh-CA (1000:1 ratio) had the most enhanced water vapor barrier and the lowest reduction in tensile strength compared to the pure HPMC film (control). In the later part of the research, the effect of …

Assessment Of Viability Of Probiotic Bacteria In Non Dairy Food Matrices Under Refrigeration Storage, Muthu Dharmasena

All Theses

Functional foods serve nutrients and physiologically active components for a healthy living. In most countries, the products related to having a healthy gut dominate the functional foods market. These products are prebiotics, probiotics and synbiotics. Concerning the health benefits, various probiotics are introduced to food matrices. Though dairy is the ideal food matrix for probiotics, the trend of non-dairy probiotics is growing among consumers.
This study included two research objectives: surveying the commercial probiotic containing products for probiotic level and developing a practical home-made probiotic fermentation process. The first part of this study was mainly based on assessing viability of …

Trapping And Control Of The Small Hive Beetle, Aethina Tumida, An Invasive Parasite Of Honey Bees, Apis Mellifera, Shannon Peterson

All Theses

The small hive beetle, Aethina tumida Murray (Coleoptera: Nitidulidae), is one of the most recent honey bee pests of economic importance, especially in the southeastern United States. Various in-hive traps have been developed to attempt to control the populations of this invasive pest within honey bee colonies. The first year of my research focused on comparing the effectiveness of three commercially available traps for removing small hive beetles. Thirty-two colonies were established with 0.9-kg package bees with a queen in four apiaries. Eight colonies were placed in each apiary, each colony randomly receiving one of four treatments: the three-chambered Hood …

Chromosomal Patterns In Populations Of The Black Fly Simulium Fibrinflatum Twinn (Diptera: Simuliidae), Kyle Parks

All Theses

Cryptic species are an important component of biodiversity, although most cryptic species have yet to be discovered. Cytogenetic studies of polytene chromosomes offer a unique level of resolution for detecting cryptic species in the family Simuliidae. Simulium fibrinflatum is a black fly morphospecies that is suspected to contain cryptic species because of its broad geographic range and variable pupal gill structure. Populations of Simulium fibrinflatum from the Saugahatchee River, AL; Anthony Shoals, GA; LaHave River, Nova Scotia; Westfield River, MA; Chauga River, SC; and Enoree River, SC, were sampled and cytogenetically analyzed to test for the presence of cryptic species. …

Functional Characterization Of A Jacalin-Like Lectin Domain-Containing Protein In Arabidopsis Thaliana, Shane Reighard

All Theses

Jacalin-related lectins (JRLs) are proteins that bind carbohydrates. Functionally, JRLs are thought to be involved in a diverse array of functions including biotic stress defense, intracellular storage, abiotic stress response, and plant development. Recent Arabidopsis thaliana microarray data indicate that a Jacalin-like domain-containing protein (JLL1) exhibits highly root specific expression. Previous transcriptomic and proteomic studies indicate that JLL1 may have a dual role in planta as a biotic stress defense protein and in plant development. In order to better understand the physiological function of JLL1 in Arabidopsis, several different analyses were conducted examining its regulatory sequences, spatial expression, responsiveness to …

Evaluation Of Use Of Em38-Mk2 As A Tool To Understand Field Scale Changes In Soil Properties, Sudershan Gangrade

All Theses

Sustainable water resources management requires tools to help farmers identify variations in soil hydraulic characteristics so that precision irrigation schemes can be developed to optimize water use. In this study we use electromagnetic induction (EMI) to evaluate whether changes in the apparent electrical conductivity (σ_a) of agricultural fields can be related to hydrologic processes. Field work for this study was completed at three different sites - 1) in different agricultural fields located in a watershed near Salri, Madhya Pradesh, India, 2) over an agricultural field located near Clemson University, SC, and 3) at a flood plain wetland restoration site near …

Drought Induced Morphological And Compositional Changes In Creeping Bentgrass (Agrostis Stolonifera Var. L. Palustris) Cuticle As It Influences Foliar Nitrogen Absorption, Frank Bethea Jr

All Theses

Creeping bentgrass is the most popular turfgrass species on golf course putting greens throughout the world due to its fine texture, recuperative ability and dense growth habit. Drought stress is an environmental induced condition that is common to turfgrasses. Foliar fertilization is a common maintenance practice that is conducted and utilized on golf course putting greens due to the reduced total input, quick response and reduced environmental impact. The cuticle of creeping bentgrass creates a hydrophobic barrier that foliar applied fertilizers need to penetrate to be used by the plant. The cuticle morphology and composition is subject to change due …

Fluid Uptake By The Lepidopteran Proboscis In Relation To Structure, Karena Kwauk

All Theses

Three species of butterflies--eastern tiger swallowtail (Papilio glaucus L.), monarch (Danaus plexippus L.), and painted lady (Vanessa cardui L.)--were used to investigate the effect that exposing multiple regions of the proboscis to fluid has on feeding rate. Although the lepidopteran proboscis historically has been considered a sealed tube with a specialized region near the tip for fluid uptake, droplets of 1% sucrose solution were shown to enter multiple locations along the proboscis. Feeding experiments were conducted comparing fluid uptake rates of butterflies with their proboscises either fully or partially submerged in 1% or 15% sucrose solutions. Only one significant relationship …

Measuring Ligand Exchange On The Surface Of Gold Nanoparticles: A Study Of Competitive Binding Of Ligands Utilizing Fluorescent Resonance Energy Transfer, Daniel D'Unger

All Theses

This study was conducted to track ligand exchange on the surface of metallic nanoparticles in order obtain a better understanding of binding strength of various functional groups. This study develops groundwork for further understanding ligand exchange as nanoparticles transition from engineered to natural systems. A problem exists in knowing the fate of these particles if they are released into natural systems, by accident or with intent. To gain a better understanding of what may occur we look at the binding strength of different ligands. This is done to gain knowledge of the possibility of displacement of ligands occurring in the …

The Social Psychology Of Evil: A Look At Abu Ghraib, Kristin Richardson

All Theses

In the spring of 2004, the military police assigned to guard the Abu Ghraib prison in Baghdad, Iraq found themselves at the center of numerous investigations regarding the abuse, torture, rape, and murder of detainees in United States custody. Their behavior was influenced and encouraged by U.S. officials, including President George W. Bush and Secretary of Defense Donald Rumsfeld. The Bush administration effectively created a reality for the military police that fostered increasingly violent and aggressive tendencies beyond what is expected or allowed in similar circumstances. Existing literature and conclusions from previous studies support the claim that social and situational …

Biomarker Effects In Sunfish And Bass From The Saluda River, Sc, Jessica Mierzejewski

All Theses

The upstate and Piedmont region of South Carolina is a rapidly urbanizing area with a fast growing population. This increase in population and development has the potential to negatively impact the aquatic system due to increased pollution from runoff and effluents from industrial, manufacturing and wastewater treatment facilities. In 2009 the Saluda River, a major river in this area of the state, was ranked 6th of America's most endangered rivers by American Rivers. This ranking was largely due to high phosphorus levels in the river, though there are many sources of pollution that may be affecting the river ecosystem. The …

Biomass And Lipid Production From Heterotrophic And Mixotrophic Fed-Batch Cultivations Of Microalgae Chlorella Protothecoides Using Glycerol, Shwetha Sivakaminathan

All Theses

Chlorella protothecoides is a microalga that can grow both photo-autotrophically and/or heterotrophically under different culture and environmental conditions. In this study both the heterotrophic growth and mixotrophic growth have been conducted. The heterotrophic experiments were conducted completely in the dark while the mixotrophic experiments had the dark cycles with periodic light exposure. The aim of the study was to independently understand the effect of each mode on biomass and lipid yields.
For the heterotrophic experiments, glycerol was used as an external organic carbon source while yeast extract was used as the nitrogen source. The carbon and nitrogen source were added …

Arsenic Affects Muscle Development And Structure In Fundulus Heteroclitus, Angela D'Amico

All Theses

Arsenic is a naturally occurring metalloid that can enter rivers and ground water. Epidemiological studies have correlated arsenic exposure with adverse developmental outcomes such as low birth weight, delays in the use of musculature, and altered locomotor activity. Previously in our lab, embryonically exposed killifish (Fundulus heteroclitus) were found to have changes in muscle development. Microarray analysis showed several genes involved in muscle development and formation altered and histological analysis showed an increase in small muscle fiber size. In this study, killifish were used to help understand if changes in muscle formation and fiber density after embryonic exposure persist, are …

The Formulation Of A Bone Targeted Drug Delivery System Of Poly(Glycolic Acid)-Poly(Ethylene Glycol) Coated Hydroxyapatite Nanoparticles For The Delivery Of Statins, Erika Jelen

All Theses

Bone is a form of mineralized connective tissue that provides strength and rigidity to the skeleton. The two primary components within bone tissue are an organic extracellular matrix, containing type I collagen, and an inorganic mineral component composed mainly of calcium phosphate hydroxyapatite crystals. Over time the microarchitecture of bone can break down due to a variety of different factors, mainly the onset of osteoporosis in post-menopausal women, Paget's disease, and the experience of a loss of gravity during space flight. Currently there are about ten million people in the United States alone suffering from osteoporosis.
The prevention of further …

Analysis Of Nanoparticle Exposure On Legionella Pneumophila Biofilm Morphology And Host-Bacteria Interactions, Tara Diane Raftery

All Theses

An increase in the amount of money spent on nanotechnology has led to an increase in funding to support nanoparticle (NP) research. Due to their stable, beneficial properties, NPs are found in daily consumer products such as bike frames, socks, cosmetics, and sunscreens. As a result of this, these NPs have the potential to enter the environment and interact with various organisms that play integral roles in the ecosystem as a whole. The effect that NPs have on aquatic systems is largely unknown and understudied. Biofilms are an important structural and functional part of aquatic ecosystems, and comprise various microorganisms …

Foraging Challenges: Unsuitable Prey And Limited Information, Travis M. Hinkelman

School of Biological Sciences: Dissertations, Theses, and Student Research

Food acquisition is a complicated task. The profitability of potential food items depends on numerous factors, including the spatial distribution, probability of detection and capture, and suitability of the food. Animals faced with such challenges can use relatively simple mechanisms to maximize foraging efficiency. However, mechanisms that maximize foraging efficiency under some ecological conditions (e.g., prey scarcity) may produce ostensibly suboptimal behavior under different ecological conditions (e.g., prey abundance). In the work presented here, we explore two facets of foraging: (1) consuming unsuitable prey, and (2) searching for resources with limited information about resource location. To explore the consequences of …

Characterization Of Binding And Fusion Efficiencies Mediated By The V1–V5 Env Derived From Transmitted And Non-Transmitted Viruses Isolated From A Perinatal Transmission Cohort From Zambia, Mackenzie Waltke

School of Biological Sciences: Dissertations, Theses, and Student Research

Human Immunodeficiency Virus Type 1 (HIV-1) is the etiological agent of acquired immunodeficiency syndrome (AIDS), which affects over 34 million people worldwide. In sub-Saharan Africa where access to antiretroviral therapies (ART) is limited, mother-to-child transmission (MTCT) rates remain high and represent a major concern in the global HIV/AIDS epidemic. Little is known about the biological properties of viruses that are transmitted perinatally, including how the biological functions of envelope (Env) influence transmissibility. Previously, transmitted viruses were found to have an advantage in replicative fitness mediated by Env V1-V5. In this study viruses derived from transmitting mother infant pairs (MIPs) were …