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Dissertations

Theses/Dissertations

2014

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Full-Text Articles in Life Sciences

Mechanisms Of Condition-Specific Regulation Of Mrna Stability By Puf Proteins: From Yeast To Humans, Joseph Russo Dec 2014

Mechanisms Of Condition-Specific Regulation Of Mrna Stability By Puf Proteins: From Yeast To Humans, Joseph Russo

Dissertations

RNA binding proteins regulate mRNA decay and translation, two key steps in the control of gene expression in cells. Controlling mRNA metabolism allows cells to respond rapidly to altering conditions by utilizing already available mRNA, bypassing the wait for newly transcribed mRNA. The Puf family of RNA binding proteins bind specific mRNAs through interactions with sequences located in the 3’ untranslated region (UTR). Puf proteins are conserved throughout eukaryotes and have diverse roles including stem cell maintenance, neuronal development, stress response and organelle biogenesis. In Saccharomyces cerevisiae, Puf proteins are conditionally regulated in response to the cells metabolic. Specifically, in …


Aminoglycoside-Induced Otoneurotoxicity: Analysis Of Inner Hair Cell Synaptic Plasticity Following Drug Exposure, Matthew M. Abernathy Dec 2014

Aminoglycoside-Induced Otoneurotoxicity: Analysis Of Inner Hair Cell Synaptic Plasticity Following Drug Exposure, Matthew M. Abernathy

Dissertations

Aminoglycoside antibiotics are powerful drugs for combating bacterial infections, but are limited in use due to their ototoxicity. This class of drug targets the auditory hair cells of the cochlea, causing cell death, which leads to a decline in auditory function. In spite of much research aimed at revealing a mechanism of damage, there are no co-therapies available to diminish the ototoxic liability of aminoglycosides. Existing research does show that there may be a neurodegenerative process that contributes to the observed toxicity. In an effort towards clarifying present understanding of issue, this dissertation project was conducted to characterize the neurodegenerative …


Ultrafast Interfacial Electron Transfer Across Molecule-Tio2 Nanocomposites: Towards Solar Cells And Two Photon Absorption, Edwin Mghanga Dec 2014

Ultrafast Interfacial Electron Transfer Across Molecule-Tio2 Nanocomposites: Towards Solar Cells And Two Photon Absorption, Edwin Mghanga

Dissertations

Interfacial charge transfer (ICT) across the molecule-TiO2 nanoparticle interface has gained enormous research attention for applications in dye sensitized solar cells (DSSC), photo-catalysis, water splitting and nonlinear optics. DSSCs are promising clean alternative energy sources. However, current DSSCs suffer from lower efficiencies and higher cost. Better understanding of the ICT processes in DSSCs can help solve these problems. We have used two strategies to understand ICT in the context of DSSCs. Firstly, we used a computationally validated anchor group, acetylacetonate (acac) to bind molecules to the semiconductor surface and facilitate charge separation. Secondly, we used natural dye sensitizers, …


Characterization Of The Early Development And Quality Of Red Snapper (Lutjanus Campechanus) Eggs And Larvae In Aquaculture Conditions, Agnès Bardon Albaret Dec 2014

Characterization Of The Early Development And Quality Of Red Snapper (Lutjanus Campechanus) Eggs And Larvae In Aquaculture Conditions, Agnès Bardon Albaret

Dissertations

The quality of red snapper Lutjanus campechanus eggs is highly variable and unpredictable in aquaculture, leading to high mortality during early larval rearing. In this work, the viability of red snapper eggs was investigated from fertilization until larvae expired due to exhaustion of vitellin reserves. The studied spawns were obtained via strip spawning wild-caught (n=17) and captive (n=7) females following hormonal induction. The fertilization rate, the hatch rate, and the duration of survival of unfed larvae post hatch were weakly correlated to each other, revealing occurrence of distinct and independent components of egg quality.

Spawns from captive females were characterized …


Clarification Of The Systematics Of The Haploporoidea (Trematoda) With Descriptions Of New Genera And Species, Michael Jay Andres Dec 2014

Clarification Of The Systematics Of The Haploporoidea (Trematoda) With Descriptions Of New Genera And Species, Michael Jay Andres

Dissertations

The superfamily Haploporoidea Nicoll, 1914 comprises two families, the Atractotrematidae Yamaguti, 1939 and the Haploporidae Nicoll, 1914, and the subfamily Cadenatellinae Gibson et Bray, 1982. All members are parasites of the alimentary tract or gall bladder of marine, estuarine, and freshwater herbivorous fishes. Overstreet and Curran (2005a) provided a review of the Haploporidae and recognized four subfamilies, the Chalcinotrematinae Overstreet et Curran, 2005, Haploporinae Nicoll, 1914, Megasoleninae Manter, 1935, and Waretrematinae Srivastava, 1937. In a series of five publications, Blasco-Costa et al. (2009a-e) revised the Haploporinae and erected a fifth subfamily, the Forticulcitinae Blasco-Costa, Balbuena, Kostadinova, et Olson, 2009. The …


Fungal Contribution To Carbon And Nutrient Cycling In A Subtropical Freshwater Marsh, Rong Su Dec 2014

Fungal Contribution To Carbon And Nutrient Cycling In A Subtropical Freshwater Marsh, Rong Su

Dissertations

Despite the well-known occurrence of emergent standing litter in freshwater marshes, very little quantitative data is available concerning the functional role and contribution of fungal decomposers to litter decomposition or their impact on ecosystem scale carbon and nutrient cycling. In the present study, microbial respiration and seasonal biomass and production rates of fungal decomposers associated with standing plant litter were examined to assess the quantitative contribution of fungi to both fine scale litter decay processes and large-scale ecosystem carbon flow pathways in a subtropical Typha domingensis and mixed Cladium jamaicense/Juncus roemarianus freshwater marsh, respectively. In addition, the growth …


Online Versus Face-To-Face Biology: A Comparison Of Student Transactional Distance, Approach To Learning, And Knowledge Outcomes, Mary Erin Riggins Dec 2014

Online Versus Face-To-Face Biology: A Comparison Of Student Transactional Distance, Approach To Learning, And Knowledge Outcomes, Mary Erin Riggins

Dissertations

Community colleges are among many other institutions increasing course offerings online, but there is still some concern about the quality of online learning. Educator concerns, a lack of empirical evidence on biology courses offered online, and the need for an equal opportunity for education support the need for clarification of the quality of distance education in biology, especially in the community college setting. Student attitudes, approaches to learning, and performance should all be studied in order to formulate a better evaluation of the quality and effectiveness of online courses (Svirko & Mellanby, 2008).

The purpose of this study was to …


Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, Gyan Sundar Sahukhal Dec 2014

Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, Gyan Sundar Sahukhal

Dissertations

Community-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immune-compromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors. The genetic basis for this enhanced virulence has yet to be determined. S. aureus possesses a wide variety of virulence factors, the expression of which is carefully coordinated by a variety of regulators. Several virulence regulators have been well characterized, but others have yet to be thoroughly investigated. Previously, the msa gene as a regulator of several virulence genes, biofilm development, and antibiotic …


Studies On The Initial Stage Of Lipid Oxidation In Bulk Oils, Elizabeth Budilarto Dec 2014

Studies On The Initial Stage Of Lipid Oxidation In Bulk Oils, Elizabeth Budilarto

Dissertations

During the oxidation of bulk oils, oxidation products (i.e. peroxide values, conjugated dienes and thiobarbituric acid reactive substances) are formed gradually and increased sharply at the end of the induction period. Tocopherols were consumed, some water was formed, and micelles increased in size during the induction period of vegetable oils oxidized in bulk. The evidence that the evolution of micellar size was in parallel with the end of induction period corroborates the recognition that micelles are the active site of oxidation. The interactions of α-tocopherol and three synergists: ascorbyl palmitate, phosphatidylcholine and L-lysine were studied in cod liver oil, to …


The Influence Of Observational Learning On Self-Reported Physical Activity, Self-Efficacy For Physical Activity, And Health-Related Fitness Knowledge For Physical Activity, Charles Gregory Bullock Dec 2014

The Influence Of Observational Learning On Self-Reported Physical Activity, Self-Efficacy For Physical Activity, And Health-Related Fitness Knowledge For Physical Activity, Charles Gregory Bullock

Dissertations

The obesity epidemic has caused tremendous burden to our economy and healthcare system. Physical activity is one method that can reduce the obesity rate. However, physical activity declines in high school and does not recover. The likelihood of adolescents continuing their involvement in physical activity depends on how they navigate the highs and lows of their physical activity experiences (Feltz & Magyar, 2006). The purpose of this study is to look at the role of observational learning in physical activity and behaviors in an adolescent population. Specifically, this research examines the influence of observational learning on self-reported physical activity, self-efficacy …


Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang Aug 2014

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …


Effects Of Animal Management Changes On The Activity Budgets And Walking Rates Of Zoo Elephants, Angela Dawn Mackey Aug 2014

Effects Of Animal Management Changes On The Activity Budgets And Walking Rates Of Zoo Elephants, Angela Dawn Mackey

Dissertations

The current study aimed to assess the effects of two management strategies, weekly rototilling of the enclosure and the provision of unpredictable foraging opportunities, on the daily behavior of six elephants housed at the San Diego Zoo. Observations took place from January to June 2013 and were conducted throughout a 24- hour period. The study was divided into three phases, each two months in duration. During the first phase (baseline) no changes were made to the current management routine of the elephants. In Phase 2, rototilling of the elephant enclosures was increased from once monthly to once per week, while …


Elucidation Of The Role Of Auxin-Input Pathways In Auxin Homeostasis., Gretchen Spiess Jul 2014

Elucidation Of The Role Of Auxin-Input Pathways In Auxin Homeostasis., Gretchen Spiess

Dissertations

Auxin is a phytohormone involved in cell elongation and division. Levels of indole-3-acetic acid (IAA), the most abundant auxin, are tightly regulated through biosynthesis, degradation, sequestration, and transport. Sequestration of IAA occurs in reversible processes by adding amino acids, polyol or simple alcohols, or sugars, forming IAA conjugates, or via a two-carbon elongation forming indole-3-butyric acid (IBA). These forms of auxin have decreased activity and are located in multiple organelles. Using a combination of molecular and genetic tools, I examined how these storage forms are working together to contribute to overall IAA levels and IAA response in both the model …


Community Organization Of Avian Malaria Parasites In Lowland Amazonia: Prevalence, Diversity, And Specialization In A Local Assemblage, Linda Maria Elenor Svensson Jun 2014

Community Organization Of Avian Malaria Parasites In Lowland Amazonia: Prevalence, Diversity, And Specialization In A Local Assemblage, Linda Maria Elenor Svensson

Dissertations

I characterized a lowland Amazonian assemblage of haemosporidian (“malaria”) parasites (Haemoproteus and Plasmodium) of understory birds by analyzing variation in prevalence (proportion of infected host individuals) among years and host species, documenting diversity of haemosporidian evolutionary lineages, and quantifying host specialization. Using standard molecular methods to screen for haemosporidia in 2488 individual birds from 104 species in the Tiputini Biodiversity Station, Ecuador, I found 21.7% to be infected. Prevalence ranged significantly among years and host species. Forty-five putative evolutionary lineages of haemosporidia were identified, by sequencing part of the cytochrome b (cyt b) gene. Based on a comparative analysis, among …


Population Genetics And Microbial Communities Of The Gopher Tortoise (Gopherus Polyphemus), Daniel Lyle Gaillard May 2014

Population Genetics And Microbial Communities Of The Gopher Tortoise (Gopherus Polyphemus), Daniel Lyle Gaillard

Dissertations

The gopher tortoise, Gopherus polyphemus, is an endangered species living in the southeastern United States. The recent and drastic decline in tortoise numbers has resulted in a multi-faceted approach to conserve this species. I used a population genetic approach to determine the population structure, genetic diversity and barriers to gene flow at a broad, regional and local scale. Tortoises are divided into five distinct genetic populations at the broad scale, the central populations have the highest levels of genetic diversity and the Tombigbee, Mobile, Apalachicola, Suwannee and St. John’s Rivers appear to be barriers to gene flow. At the regional …


The Delivery, Speciation, And Fate Of Trace Elements In St. Louis Bay, Mississippi, Gopal Bera May 2014

The Delivery, Speciation, And Fate Of Trace Elements In St. Louis Bay, Mississippi, Gopal Bera

Dissertations

Estuaries are dynamic regions in which there can be significant modification of the riverine flux of trace elements to the open ocean due to various geochemical, physical, and biological processes. Additionally, estuaries are often subject to anthropogenic inputs of trace elements. The first portion of this study investigated the source, behavior, and sediment interaction of anthropogenic stable cesium (Cs) in St. Louis Bay (SLB), MS. A consistent increase in stable Cs concentration was noticed in sediment cores starting from a period when a titanium dioxide refinery on SLB started operations. Weak correlation between Cs and clay percentage and strong correlations …


Biogeochemistry Of Trace Elements In The Mixing Zone Of The Mississippi And Atchafalaya Rivers And Chemical Distributions As Affected By The Deepwater Horizon Blowout, Dongjoo Joung May 2014

Biogeochemistry Of Trace Elements In The Mixing Zone Of The Mississippi And Atchafalaya Rivers And Chemical Distributions As Affected By The Deepwater Horizon Blowout, Dongjoo Joung

Dissertations

Selected trace elements (TEs), dissolved organic carbon, and nutrients were studied in Louisiana Shelf waters including the Mississippi (MR) and Atchafalaya (AR) River plumes during periods of high, intermediate, and low river discharges. Seasonal variations in TEs were observed at low salinity, reflecting seasonal changes in the river water endmembers. Shelf surface water dissolved Mo, Cs, U, Ni, and Cu showed conservative behavior with minor scattering in some high salinity waters. Based on associated mixing experiments, nutrient and chlorophyll distributions, as well as surface-bottom concentration contrasts, the non-conservative behavior of TEs was variously related to colloidal flocculation (Fe, Cr), biological …


Revision Of 13 Genera Of Haploporidae (Trematoda), Eric Edward Pulis May 2014

Revision Of 13 Genera Of Haploporidae (Trematoda), Eric Edward Pulis

Dissertations

The Haploporidae is a family of digeneans united by the combination of the possession of a hermaphroditic sac and a single testis or, rarely, two tandem testes. The major divisions in the Haploporidae have been based on the organization, development, and nature of the male and female reproductive systems. Overstreet and Curran (2005) has been the only attempt to organize the genera of the Haploporidae in a subfamilial framework. In the present work the validity of the subfamily Waretrematinae by Overstreet and Curran (2005) is assessed by morphological and molecular methods, based on original descriptions, type and vouchered, specimens and …


Identification Of Novel Natural Compounds With Anti-Breast Cancer Activities, Yusra Saif Al Dhaheri May 2014

Identification Of Novel Natural Compounds With Anti-Breast Cancer Activities, Yusra Saif Al Dhaheri

Dissertations

Breast cancer continues to be the leading cause of cancer-related death in women worldwide. In this dissertation, natural compounds with anti-breast cancer activities were identified. We investigated the effect of Salinomycin, a potassium ionophore isolated from Streptomyces albus, on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231. High concentrations of Salinomycin induced a G2 arrest, down regulation of survivin and triggered apoptosis. Interestingly, treatments with low concentrations of Salinomycin induced a transient G1 arrest at an earlier time and G2 arrest and senescence, associated with enlarged cell morphology, at a later time. There was also …


Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai Jan 2014

Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai

Dissertations

Prostaglandin F2α (PGF2α) is a potent physiological inhibitor of adipocyte differentiation. In previous studies, we demonstrated that PGF2α inhibits adipogenesis via activation of the calcium-regulated protein phosphatase, calcineurin. In this current study, we have now extended these findings to identify the IL-11 cytokine and the Nurr1 orphan nuclear hormone receptor as functionally important downstream transcriptional targets of the PGF2α/calcineurin-pathway involved in the inhibition of adipocyte differentiation. In the case of IL-11, we show that this cytokine acts in an autocrine fashion to inhibit adipogenesis via the essential actions of the gp130 cytokine co-receptor signaling subunit. Further, by using a well-characterized …


Host Entry Factors For Human Coronaviruses, Taylor Heald-Sargent Jan 2014

Host Entry Factors For Human Coronaviruses, Taylor Heald-Sargent

Dissertations

Coronaviruses infect a diverse range of animals from birds to pigs and cats to humans. Coronaviruses employ RNA-based replicative processes and as such are genetically adaptable to acquire novel host ranges. A coronavirus from one species can jump to another by shifting its entry requirements. As we learned from the Severe Acute Respiratory Syndrome (SARS) pandemic, this shift in species can have detrimental consequences. Thus, it is imperative that we understand the virus-host interaction during the entry process.

This dissertation focuses on host entry factors that influence human coronavirus entry. Recently, a new class of proteases, the type II transmembrane …


Adenovirus Vectors As Potent Adjuvants In Vaccine Development, Kathleen Ann Mcguire Jan 2014

Adenovirus Vectors As Potent Adjuvants In Vaccine Development, Kathleen Ann Mcguire

Dissertations

Due to their ability to activate the immune system, replication-defective Adenoviruses (Ad) are potential vaccine vectors for several pathogens. The proinflammatory response to Ad contributes to the response to vaccine antigens. We found that reactive oxygen species (ROS) are an important signal in the proinflammatory response to Ad. We identified that serotype 5 adenovirus (Ad5) elicits ROS by inducing mitochondrial membrane damage, a process that is dependent on endosomal membrane rupture and Cathepsin release. This mitochondrial dysfunction contributes to NLRP3 inflammasome- and NFκB-dependent innate immune activation. The ROS-dependent inflammatory response likely contributes to the adaptive immune response by supporting DC …


The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott Jan 2014

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …


Identifying Novel Factors Involved In Biofilm Formation By Vibrio Fischeri, Valerie Ray Jan 2014

Identifying Novel Factors Involved In Biofilm Formation By Vibrio Fischeri, Valerie Ray

Dissertations

Biofilm formation by bacteria provides them with a means to survive harsh environmental conditions and promote colonization of a particular surface (biotic or abiotic). Due to the resistance properties of biofilms, biofilm-forming bacteria are difficult to treat in the context of host infections. Thus, investigating the processes that control biofilm formation will promote the development of novel therapeutics. To study biofilm formation in the context of a host, I utilized as a model system the marine bacterium Vibrio fischeri, which must be competent to form a biofilm to colonize its squid host Euprymna scolopes. Biofilm formation by V. fischeri requires …


Haploinsufficiency Of Cardiac Myosin Binding Protein-C In The Development Of Hypertrophic Cardiomyopathy, David Barefield Jan 2014

Haploinsufficiency Of Cardiac Myosin Binding Protein-C In The Development Of Hypertrophic Cardiomyopathy, David Barefield

Dissertations

Heart Failure is one of the leading causes of morbidity and mortality in the human population and represents a common endpoint for several diseases including inherited cardiomyopathies. Hypertrophic Cardiomyopathy (HCM) is characterized by left ventricular wall thickening, diastolic dysfunction, and sarcomere disarray. Mutations in sarcomeric protein encoding genes have been established as causative for HCM.

The gene MYBPC3, encoding cardiac myosin binding protein-C (cMyBP-C), is the second most commonly mutated gene in HCM cases. As a majority of these mutations have been determined to result in a null allele which does not produce any protein, it is thought that haploinsufficiency …


Mutations In Phospholamban Alter The Structure And Function Of The Calcium Atpase Regulatory Complex, Neha Abrol Jan 2014

Mutations In Phospholamban Alter The Structure And Function Of The Calcium Atpase Regulatory Complex, Neha Abrol

Dissertations

Phospholamban (PLB) is an integral membrane protein that plays an important role in regulation of cardiac calcium handling and contractility. PLB exists as a homopentamer in the membrane, which upon deoligomerization into active monomers reversibly inhibits sarco/endoplasmic reticulum calcium ATPase (SERCA). Mutations in PLB that change the PLB monomer-pentamer equilibrium result in dysregulation of SERCA. To determine the structural and regulatory role of the C-terminal residues of PLB in the membranes of living cells, we fused fluorescent protein tags to PLB and SERCA. We then studied the effect of C-terminal alanine substitutions and truncation mutations on PLB oligomerization and SERCA …


Catalytic Mechanism And Maturation Of The Metalloenzyme Nitrile Hydratase, Natalie I. Gumataotao Jan 2014

Catalytic Mechanism And Maturation Of The Metalloenzyme Nitrile Hydratase, Natalie I. Gumataotao

Dissertations

Nitrile hydratases are metalloenzymes that catalyze the hydration of nitriles to their corresponding amides in a specific manner at ambient pressures and temperatures at neutral pH. Traditional industrial methods require high temperature and pressure, extreme pH, and heavy metals. NHases are used as biocatalysts in the large scale industrial production of amide precursors to textiles, animal feedstock, and polymers. Notably, NHase is used in the production of ~100,000 tons of acrylamide annually by the Mitsubishi Corporation.

Despite being used extensively in industry, questions remain about NHase. The catalytic mechanism is not defined. Understanding the way in which the nitrile is …


Identification And Analysis Of Omentum Derived Suppressor Cells In Regards To Th17 Inhibition, Nick Huang Jan 2014

Identification And Analysis Of Omentum Derived Suppressor Cells In Regards To Th17 Inhibition, Nick Huang

Dissertations

Omentum has been harnessed by surgeons for hundreds of years, providing an ideal environment for graft healing and acceptance. However, little is known about the cellular mechanisms that promote the tolergenic environment of the omentum. We examined the cellular composition and role of activated omentum in regards to T-cell immunomodulation. We then tested activated omentum as a cellular therapy in a mouse allogenic lung transplantation model.

Our findings demonstrated activated omentum is mostly comprised of non-hematopoietic cells resembling mesenchymal stem-like cells (MSCs) and myeloid derived suppressor cells (MDSCs). Activated omentum exhibited anti-inflammatory properties through suppression of Th1 and Th17, while …


Coronavirus Proteases As Therapeutic Targets: Development Of Biosensors To Detect Inhibition Of Protease Activity And Separation Of The Multiple Functions Of Coronavirus Papain-Like Proteases, Andrew Kilianski Jan 2014

Coronavirus Proteases As Therapeutic Targets: Development Of Biosensors To Detect Inhibition Of Protease Activity And Separation Of The Multiple Functions Of Coronavirus Papain-Like Proteases, Andrew Kilianski

Dissertations

Coronaviruses are important human pathogens and have the potential to severely impact public health on an international scale. The emergence of SARS-CoV and MERS-CoV highlight the need for research to identify antivirals and vaccines against coronaviruses. To develop therapeutics against current and potentially emergent coronaviruses, I utilized two approaches targeting the proteases encoded within all coronaviruses. The papain-like protease and 3C-like protease of coronaviruses are responsible for cleaving viral polyproteins early during infection, and this step is required for viral replication. To quantitatively assess the inhibition by small-molecule compounds on MERS-CoV protease activity, I developed a luciferase-based biosensor to monitor …


The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken Jan 2014

The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken

Dissertations

The AF9 protein is one of the most common chromosomal translocation partners of the MLL gene in MLL leukemia. Wild-type AF9 is a member of the pTEFb transcription elongation complex, and interacts with gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are retained in the oncogenic MLL-AF9 fusion protein, and may be required for leukemic transformation.

Using bone marrow progenitor cells isolated from conditional Af9 knockout mice, we examined in vitro differentiation of hematopoietic progenitor cells to the erythroid, myeloid and megakaryocytic lineages in the presence or absence of Af9. Based on previously published studies, we …