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Full-Text Articles in Molecular Biology

Cargo Transport By Myosin Va Molecular Motors Within Three-Dimensional In Vitro Models Of The Intracellular Actin Cytoskeletal Network, Andrew Thomas Lombardo Jan 2018

Cargo Transport By Myosin Va Molecular Motors Within Three-Dimensional In Vitro Models Of The Intracellular Actin Cytoskeletal Network, Andrew Thomas Lombardo

Graduate College Dissertations and Theses

Intracellular cargo transport involves the movement of critical cellular components (e.g. vesicles, organelles, mRNA, chromosomes) along cytoskeletal tracks by tiny molecular motors. Myosin Va motors have been demonstrated to play a vital role in the transport of cargos destined for the cell membrane by navigating their cargos through the three-dimensional actin networks of the cell. Transport of cargo through these networks presents many challenges, including directional and physical obstacles which teams of myosin Va-bound to a single cargo must overcome. Specifically, myosin Va motors are presented with numerous actin-actin intersections and dense networks of filaments which can act as ...


Detection Of The Lung Environment By Multi-Drug Resistant Gram-Negative Bacterial Pathogens, Graham Geier Willsey Jan 2018

Detection Of The Lung Environment By Multi-Drug Resistant Gram-Negative Bacterial Pathogens, Graham Geier Willsey

Graduate College Dissertations and Theses

Nosocomial lung infections are a growing concern in the United States, with more than 300,000 cases reported annually. More than 30 % of which are caused by the Gram-negative bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae. Similarly, Gram-negative bacteria establish chronic infections in individuals with cystic fibrosis (CF) that are difficult or impossible to eradicate.P. aeruginosa has historically been one of the most prevalent pathogens of adults with CF. However, as antipseudomonal therapy has improved, more antibiotic resistant species have taken hold, including Stenotrophomonas maltophilia, which now colonizes more than 10 % of individuals with CF. Regardless of the cause or ...


Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald Jan 2018

Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald

Graduate College Dissertations and Theses

In the United States, metastatic breast cancer kills approximately 40,000 women and 400 men annually, and approximately 200,000 new cases of breast cancer are diagnosed each year. Worldwide, breast cancer is the leading cause of cancer deaths among women. Despite advances in the detection and treatment of metastatic breast cancer, mortality rates from this disease remain high because the fact is that once metastatic, it is virtually incurable. It is widely accepted that a major reason breast cancer continues to exhibit recurrence after remission is that current therapies are insufficient for targeting and eliminating therapy-resistant cancer cells. Emerging ...


Target Identification Strategies For Mmv Malaria Box Inhibitors Of Toxoplasma Gondii Growth, Jenna Elizabeth Foderaro Jan 2017

Target Identification Strategies For Mmv Malaria Box Inhibitors Of Toxoplasma Gondii Growth, Jenna Elizabeth Foderaro

Graduate College Dissertations and Theses

Small molecule screening is commonly used to discover lead compounds for drug development, but it can also be a powerful way to identify chemical probes for studying biological mechanisms. Our lab uses small molecules to study the mechanisms by which the protozoan parasite Toxoplasma gondii infects and replicates within its hosts. In this work, we employed a fluorescence-based assay to screen the Medicines for Malaria Venture (MMV) Open Access Malaria box for compounds that affect T. gondii growth. The box contains 400 previously identified small-molecule inhibitors of the related parasite, Plasmodium falciparum. We identified 79 hits, including a 2,4-diaminoquinazoline ...


Molecular Mechanisms Of Mrna Transport By A Class V Myosin And Cytoplasmic Dynein, Thomas Edward Sladewski Jan 2017

Molecular Mechanisms Of Mrna Transport By A Class V Myosin And Cytoplasmic Dynein, Thomas Edward Sladewski

Graduate College Dissertations and Theses

mRNA localization ensures correct spatial and temporal control of protein synthesis in the cell. Using a single molecule in vitro approach, we provide insight into the mechanisms by which localizing mRNAs are carried by molecular motors on cytoskeletal tracks to their destination.

Budding yeast serves as a model system for studying the mechanisms of mRNA transport because localizing mRNAs are moved on actin tracks in the cell by a single class V myosin motor, Myo4p. Molecular motors that specialize in cargo transport are generally double-headed so that they can "walk" for many microns without dissociating, a feature known as processivity ...


Silica Nanoparticles For The Delivery Of Dna And Rnai In Cancer Treatment, Michael Aaron Vrolijk Jan 2017

Silica Nanoparticles For The Delivery Of Dna And Rnai In Cancer Treatment, Michael Aaron Vrolijk

Graduate College Dissertations and Theses

DNA and interfering RNA (RNAi) – short interfering RNA (siRNA) and micro RNA (miRNA) – are promising new cancer therapies, especially for drug resistant lines. However, they require a delivery system in vivo to prevent degradation and off target effects. Silica based nanoparticles, both solid and mesoporous, are a promising option due to their biocompatibility, ease of preparation and morphology control, reproducibility, and facile addition of functional groups including targeting ligands.

After a brief introduction to cancer treatment and review of the current nanoparticle treatments undergoing clinical trials, this thesis details the many methods explored over the past ten years to fine-tune ...


Rumen Microbial Ecology And Rumen-Derived Fatty Acids: Determinants Of And Relationship To Dairy Cow Production Performance, Laura Marie Cersosimo Jan 2017

Rumen Microbial Ecology And Rumen-Derived Fatty Acids: Determinants Of And Relationship To Dairy Cow Production Performance, Laura Marie Cersosimo

Graduate College Dissertations and Theses

Rumen microbiota enable dairy cattle to breakdown fiber into useable energy for milk production. Rumen bacteria, protozoa, and fungi ferment feedstuff into volatile fatty acids (VFA), the main energy source, while methanogens utilize fermentation by-products to produce methane. Milk fat contains several bioactive rumen-derived fatty acids (FA), including odd-chain FA (OCFA) and branched-chain FA (BCFA), important for maintenance of human health. The overarching dissertation goal was to determine which factors affect rumen methanogen and protozoal community structures and their metabolism products, while defining relationships between rumen microbiota and animal performance. Results presented contribute to the goals of providing new knowledge ...


The Role Of Inflammasomes In Asbestos-Induced Mesothelial To Fibroblastic Transition, Joyce K. Thompson Jan 2017

The Role Of Inflammasomes In Asbestos-Induced Mesothelial To Fibroblastic Transition, Joyce K. Thompson

Graduate College Dissertations and Theses

Malignant Mesothelioma (MM) is a fatal disease with a low median survival between 8 to 12 months after diagnosis. MM has a long latency period (10-60 years), is causally related to asbestos exposure, and is refractory to all available modes of therapy. Despite the causal association between asbestos exposure and MM however, the mechanisms by which asbestos induces this deadly disease remain unclear. Chronic inflammation due to the presence of asbestos fibers is believed to play an important role in all aspects of MM pathogenesis, from development to progression and resistance. Chronic inflammation has been shown to promote dysregulated wound ...


Epicardial Cell Engraftment And Signaling Promote Cardiac Repair After Myocardial Infarction, Krithika Rao Jan 2016

Epicardial Cell Engraftment And Signaling Promote Cardiac Repair After Myocardial Infarction, Krithika Rao

Graduate College Dissertations and Theses

The epicardium is a single layer of epithelial (mesothelial) cells that covers the entire heart surface, but whose function in adult mammals is poorly understood. Defining the role of epicardial cells during homeostasis, growth and injury has potential to provide new treatment strategies for human diseases that result in heart failure, due to extensive loss of viable cardiac tissue. We hypothesized that epicardial cells contribute to repair as transplantable progenitor cells for cellular regeneration and as a source of secreted growth factors for cell protection after myocardial infarction.

Adult epicardial cells were prospectively isolated as uncommitted epithelial cells using epithelial-specific ...


Functional Consequences Of Ama1-Ron2 Interaction During Host Cell Invasion By Toxoplasma., Shruthi Krishnamurthy Jan 2016

Functional Consequences Of Ama1-Ron2 Interaction During Host Cell Invasion By Toxoplasma., Shruthi Krishnamurthy

Graduate College Dissertations and Theses

T.gondii is a model organism of the phylum Apicomplexa that infects one third of the human population. While the majority of infections are asymptomatic or manifest with mild flu-like symptoms, toxoplasmosis can be fatal in immunocompromised individuals and in the developing fetus. The lytic cycle of tachyzoite-stage parasites causes damage to the host by repeated rounds of host cell invasion, intracellular replication and lysis of the host cell upon egress.

Invasion is a key step for the parasite to maintain its intracellular lifestyle. Apical Membrane Antigen 1 (AMA1) is an adhesin released from a unique set of secretory organelles ...


Barcoding The Actin Track: Differential Regulation Of Myosin Motors By Tropomyosin, Joseph Emerson Clayton Jan 2016

Barcoding The Actin Track: Differential Regulation Of Myosin Motors By Tropomyosin, Joseph Emerson Clayton

Graduate College Dissertations and Theses

Myosins and tropomyosins represent two types of actin filament-associated proteins that often work together in contractile and motile processes in the cell. While the role of thin filament troponin-tropomyosin complexes in regulating striated muscle myosin II is well characterized, the role of tropomyosins in non-muscle myosin regulation is not well understood. Fission yeast has recently proved to be a useful model with which to study regulation of myosin motors by tropomyosin owing to its tractable genetics, well-defined actin cytoskeleton, and established actin biochemistry.

A hallmark of type V myosins is their processivity -- the ability to take multiple steps along actin ...


Mechanisms And Dynamics Of Oxidative Dna Damage Repair In Nucleosomes, Wendy J. Cannan Jan 2016

Mechanisms And Dynamics Of Oxidative Dna Damage Repair In Nucleosomes, Wendy J. Cannan

Graduate College Dissertations and Theses

DNA provides the blueprint for cell function and growth, as well as ensuring continuity from one cell generation to the next. In order to compact, protect, and regulate this vital information, DNA is packaged by histone proteins into nucleosomes, which are the fundamental subunits of chromatin. Reactive oxygen species, generated by both endogenous and exogenous agents, can react with DNA, altering base chemistry and generating DNA strand breaks. Left unrepaired, these oxidation products can result in mutations and/or cell death. The Base Excision Repair (BER) pathway exists to deal with damaged bases and single-stranded DNA breaks. However, the packaging ...


Analysis Of Function Of The Son1-Interacting Protein, Lnk2 In Arabidopsis Thaliana, Prince Kudjoe Zogli Jan 2015

Analysis Of Function Of The Son1-Interacting Protein, Lnk2 In Arabidopsis Thaliana, Prince Kudjoe Zogli

Graduate College Dissertations and Theses

The Arabidopsis SON1 F-box protein was implicated in regulating a pathogen defense pathway, but its exact function in wild-type plants is unknown. As an F-box protein it was predicted that SON1 would assembles into a SON1-SCF ubiquitin ligase complex that recruits specific plant defense-related proteins for proteolysis. The yeast 2-hybrid assay was used to screen for potential substrates for a putative SON1-SCF ligase, leading to the identification of Arabidopsis LNK2 as a SON1-binding factor.

Comprehensive protein-protein interaction analysis has shown that the binding of SON1 to LNK2 protein is specific, because closely related, full-length Arabidopsis F-box proteins do not interact ...


Dna Glycosylases Remove Oxidized Base Damages From G-Quadruplex Dna Structures, Jia Zhou Jan 2015

Dna Glycosylases Remove Oxidized Base Damages From G-Quadruplex Dna Structures, Jia Zhou

Graduate College Dissertations and Theses

The G-quadruplex DNA is a four-stranded DNA structure that is highly susceptible to oxidation due to its G-rich sequence and its structure. Oxidative DNA base damages can be mutagenic or lethal to cells if they are left unrepaired. The base excision repair (BER) pathway is the predominant pathway for repair of oxidized DNA bases. DNA glycosylases are the first enzymes in BER and are responsible for removing base lesions from DNA. How DNA glycosylases remove base lesions from duplex and single-stranded DNA has been intensively studied, while how they act on G-quadruplex DNA remains to be explored.

In Chapter II ...


A Comparative Analysis Of The Moose Rumen Microbiota And The Pursuit Of Improving Fibrolytic Systems., Suzanne Ishaq Pellegrini Jan 2015

A Comparative Analysis Of The Moose Rumen Microbiota And The Pursuit Of Improving Fibrolytic Systems., Suzanne Ishaq Pellegrini

Graduate College Dissertations and Theses

The goal of the work presented herein was to further our understanding of the rumen microbiota and microbiome of wild moose, and to use that understanding to improve other processes. The moose has adapted to eating a diet of woody browse, which is very high in fiber, but low in digestibility due to the complexity of the plant polysaccharides, and the presence of tannins, lignin, and other plant-secondary compounds. Therefore, it was hypothesized that the moose would host novel microorganisms that would be capable of a wide variety of enzymatic functions, such as improved fiber breakdown, metabolism of digestibility-reducing or ...


A Novel Approach For The Identification Of Cytoskeletal And Adhesion A-Kinase Anchoring Proteins, Laura Taylor Director Jan 2014

A Novel Approach For The Identification Of Cytoskeletal And Adhesion A-Kinase Anchoring Proteins, Laura Taylor Director

Graduate College Dissertations and Theses

A-kinase anchoring proteins (AKAPs) are signaling scaffolds which provide spatial and temporal organization of signaling pathways in discrete subcellular compartments. Through tethering the cyclic-AMP dependent protein kinase A (PKA), AKAPs target PKA activity to distinct regions in the cell, bringing PKA in close proximity to its target proteins. This provides a high level of specificity and regulation of PKA and its role in mediating a number of biological processes, one of which is cell migration. Cell migration is a highly dynamic and fundamental process, when misregulated can lead to a number of pathologies. The process of cell migration requires integration ...


Role Of Heme Oxygenase In Modulating Expression Of Ros-Regulatory Enzymes In Medicago Truncatula, Parna Ghosh Jan 2014

Role Of Heme Oxygenase In Modulating Expression Of Ros-Regulatory Enzymes In Medicago Truncatula, Parna Ghosh

Graduate College Dissertations and Theses

Heme Oxygenase (HO) is an enzyme universally found in animals, plants and microbes. In plants, the role of heme oxygenase in the synthesis of the phytochrome chromophore is well recognized and has been extensively studied; however its role in regulating reactive oxygen species (ROS) in plants is just beginning to be explored, particularly in legumes. Legumes interact with Rhizobium bacteria to form symbiotic nitrogen fixing nodules. ROS plays an important role in the development of roots as well as symbiotic nodules. In the model legume Medicago truncatula, ROS in the root is regulated in part by the LATD/NIP gene ...


Helicase-Ssb Interactions In Recombination-Dependent Dna Repair And Replication, Christian Jordan Jan 2014

Helicase-Ssb Interactions In Recombination-Dependent Dna Repair And Replication, Christian Jordan

Graduate College Dissertations and Theses

Dda, one of three helicases encoded by bacteriophage T4, has been well- characterized biochemically but its biological role remains unclear. It is thought to be involved in origin-dependent replication, recombination-dependent replication, anti- recombination, recombination repair, as well as in replication fork progression past template-bound nucleosomes and RNA polymerase. One of the proteins that most strongly interacts with Dda, Gp32, is the only single-stranded DNA binding protein (SSB) encoded by T4, is essential for DNA replication, recombination, and repair.

Previous studies have shown that Gp32 is essential for Dda stimulation of replication fork progression. Our studies show that interactions between Dda ...


Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation, Xiaozheng Song Jan 2014

Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation, Xiaozheng Song

Graduate College Dissertations and Theses

The mammary gland cell growth and differentiation are under the control of both systemic hormones and locally produced growth factors. Among all these important hormones and growth factors, estrogen plays a central role in mammary gland development. The biological function of estrogen is mediated by estrogen receptor α (ERα) and estrogen receptor β (ERβ). Both ERα and ERβ are expressed in the mammary gland, but with distinct expression patterns. In the mammary gland, ERα has been proved to be the estrogen receptor that mediates the mitogenic function of estrogen. However the function of ERβ in mammary cell proliferation is less ...


Mitochondrial Structure And Function As A Therapeutic Target In Malignant Mesothelioma, Brian Cunniff Jan 2014

Mitochondrial Structure And Function As A Therapeutic Target In Malignant Mesothelioma, Brian Cunniff

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a rare tumor associated with occupational exposure to asbestos with no effective treatment regime. Evaluation of mitochondrial function in human MM cell lines revealed a common tumor phenotype: in comparison to immortalized or primary human mesothelial cells, MM tumor cells displayed a more oxidized mitochondrial environment, increased expression of mitochondrial antioxidant enzymes, and altered mitochondrial metabolism. Earlier work by our laboratory indicated that increases in mitochondrial reactive oxygen species (mROS) in MM cell lines supports expression of FOXM1, an oncogenic transcription factor that contributes to increased cell proliferation and chemoresistance. These studies sought to investigate targeting ...


Regulation Of Β-Casein Gene Expression By Octamer Transcription Factors And Utilization Of Β-Casein Gene Promoter To Produce Recombinant Human Proinsulin In The Transgenic Milk, Xi Qian Jan 2014

Regulation Of Β-Casein Gene Expression By Octamer Transcription Factors And Utilization Of Β-Casein Gene Promoter To Produce Recombinant Human Proinsulin In The Transgenic Milk, Xi Qian

Graduate College Dissertations and Theses

β-Casein is a major milk protein, which is synthesized in mammary alveolar secretory epithelial cells (MECs) upon the stimulation of lactogenic hormones, mainly prolactin and glucocorticoids (HP). Previous studies revealed that the proximal promoter (-258 bp to +7 bp) of the β-casein gene is sufficient for induction of the promoter activity by HP. This proximal region contains the binding sites for the signal transducer and activator of transcription 5 (STAT5), glucocorticoid receptor (GR), and octamer transcription factors (Oct). STAT5 and GR are essential downstream mediators of prolactin and glucocorticoid signaling, respectively. This study investigated the functions of Oct-1 and Oct-2 ...