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Full-Text Articles in Molecular Biology

A Novel Cytokine Response Modulatory Function Of Mek Inhibitors Mediates Therapeutic Efficacy, Mengyu Xie Nov 2019

A Novel Cytokine Response Modulatory Function Of Mek Inhibitors Mediates Therapeutic Efficacy, Mengyu Xie

Graduate Theses and Dissertations

Despite the recent success of immune-checkpoint blockade therapy for late-stage non-small cell lung cancer (NSCLC), lung cancer is still the leading cause of cancer deaths worldwide. One of the most important characteristics of lung cancer in therapeutic decision-making are the targetable molecules, including EGFR, ALK, BRAF, and MEK. The excitement of immune-checkpoint blockade therapy has triggered concerted efforts that focus on exploring combinations of immune checkpoint therapy with other approved therapeutic regimens aiming at further augmenting positive outcomes and survival. However, the lack of understanding of underlying mechanisms and evidence-based clinical testing has hindered the progress to a cure. Hence ...


Modeling Of Interaction Of Ions With Ether- And Ester-Linked Phospholipids, Matthew W. Saunders Oct 2019

Modeling Of Interaction Of Ions With Ether- And Ester-Linked Phospholipids, Matthew W. Saunders

Graduate Theses and Dissertations

Phospholipids are present in all parts of cells and are used in many signalling and struc- tural roles. As structural molecules they act as the main component of cellular membranes. Bilayer properties are heavily influenced by the structure of their component polar lipids, and different lipids are found in different organisms. A distinguishing feature of Archaeal plasma membranes is that their phospholipids contain ether-links, as opposed to bacterial and eukaryotic plasma membranes where phospholipids primarily contain ester-links. In our work we examine the effects of salt on bilayer structure in the case of both ester- and ether-linked lipid bilayers. We ...


Novel Strategies On Characterizing Biologically Specific Protein-Protein Interaction Networks, Bi Zhao Jul 2019

Novel Strategies On Characterizing Biologically Specific Protein-Protein Interaction Networks, Bi Zhao

Graduate Theses and Dissertations

The function, behavior, and environmental response of biological systems are essentially determined by the complex interaction and regulation of biomolecules inside the systems. Therefore, it is critical to characterize the inter-molecular interaction and regulation of biomolecules inside these systems. In this direction, many experimental techniques have been developed and these techniques have been used in many different model systems under various conditions. Consequently, a massive amount of data has been generated. These data cover multiple aspects of molecular interaction and regulation, such as protein-protein interaction, microRNA-RNA interaction, gene expression profiles, etc. While carrying rich information, these data may also contain ...


Intrinsically Disorder Proteins And Liquid-Liquid Phase Transitions In Neurodegenerative Diseases, April Lynn Darling Jul 2019

Intrinsically Disorder Proteins And Liquid-Liquid Phase Transitions In Neurodegenerative Diseases, April Lynn Darling

Graduate Theses and Dissertations

Neurodegenerative diseases have a negative impact on health and economics, effecting more than 20 million people in the United States and costing around $800 billion in 2018. Additionally, most neurodegenerative diseases such as Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and several others are fatal and have no cure or effective treatment. Many of these diseases have a common theme of protein aggregates being present in disease tissue. These aggregates are thought to be toxic to the cell and prevention of pathological aggregation and elimination of these cellular aggregates may serve as a potential therapeutic approach ...


Targeting Pten For Therapy In Cancer And Ptenopathies, Emily Palumbo Jul 2019

Targeting Pten For Therapy In Cancer And Ptenopathies, Emily Palumbo

Graduate Theses and Dissertations

PTEN, a dual protein and lipid phosphatase, regulates a myriad of cellular functions including PI3K pathway signaling, cell migration, proliferation, invasion and apoptosis. PTEN mutations often lead to multiple malignancies, including prostate, breast, endometrial, skin and brain cancers, associated with hyperactive PI3K signaling. PTEN mutations have also been associated with a variety of other diseases, classified as PTEN Hamartoma Tumor Syndromes (PHTS). In addition, compromised function or reduced expression of PTEN due to non-genomic mechanisms are associated with many types of hyperproliferative diseases, such as restenosis and neoplastic diseases, including melanoma, lung, breast, prostate and colon cancers. Although PI3K pathway ...


Roux-En-Y Gastric Bypass Attenuates Obesity-Related Liver Injury, Drew Alan Rideout Jul 2019

Roux-En-Y Gastric Bypass Attenuates Obesity-Related Liver Injury, Drew Alan Rideout

Graduate Theses and Dissertations

Obesity is a growing epidemic in the United States with significant co-morbidities. Non-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent manifestation of obesity that can lead to cirrhosis. Roux-en-Y gastric bypass (RYGB) results in substantial long-term weight loss and resolution of obesity-related metabolic diseases. There appears to be a weight-independent molecular mechanism for the improvement of diabetes mellitus and NAFLD after RYGB, which is poorly understood. Obesity is associated with chronic inflammation that accompanies the hepatic steatosis. Through unknown mechanisms, RYGB in humans increases serum levels of the fat-derived adipocytokine, adiponectin. Adiponectin (an anti-inflammatory cytokine) is known to have a ...


Functional Characterization Of The Ovarian Tumor Domain Deubiquitinating Enzyme 6b, Jasmin M. D'Andrea Jun 2019

Functional Characterization Of The Ovarian Tumor Domain Deubiquitinating Enzyme 6b, Jasmin M. D'Andrea

Graduate Theses and Dissertations

The posttranslational modification ubiquitination is major regulatory mechanism used throughout cell signaling pathways such as cell cycle regulation and the DNA damage response. As such, the E3 ligases and their deubiquitinating enzyme counterparts, which conjugate and deconjugate ubiquitin to and from protein substrates respectively, must be tightly regulated to prevent aberrant cellular behaviors that could lead to diseases such as cancer.

Of the five families of deubiquitinating enzymes, the Ovarian Tumor Domain (OTU) family is fairly unique and under-studied; many of its family members hold a linkage specificity to certain ubiquitin chains and a number of them have been implicated ...


Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri Apr 2019

Novel Insights Into The Multifaceted Roles Of Blm In The Maintenance Of Genome Stability, Vivek M. Shastri

Graduate Theses and Dissertations

Genomic instability is a hallmark of disorders in which DNA replication and repair genes are dysfunctional. The tumor suppressor RECQ helicase gene BLM encodes the 3’-5’ DNA Bloom syndrome helicase BLM, which plays important roles during DNA replication, recombination and repair to maintain genome stability. Mutations within BLM cause Bloom syndrome, an autosomal recessive disorder characterized by growth defects, immunodeficiency, >10-fold higher sister chromatid exchange compared to normal cells, and an increased predisposition to a wide range of cancers from an early age. Single nucleotide polymorphisms or SNPs in BLM have been reported to be associated with susceptibility to ...


Role Of Oncogenic Protein Kinase C-Iota In Melanoma Progression; A Study Based On Atypical Protein Kinase-C Inhibitors, Wishrawana Sarathi Bandara Ratnayake Mar 2019

Role Of Oncogenic Protein Kinase C-Iota In Melanoma Progression; A Study Based On Atypical Protein Kinase-C Inhibitors, Wishrawana Sarathi Bandara Ratnayake

Graduate Theses and Dissertations

Irrespective of plentiful efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 30 years, thus greatly affecting public health and the economy. We have investigated the effects of five novel aPKC inhibitors; 2-acetyl-1,3-cyclopentanedione (ACPD), 3,4-Diaminonaphthalene-2,7-disulfonic acid (DNDA), [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocyte cell ...


Advanced Proteomic And Epigenetic Characterization Of Ethanol-Induced Microglial Activation, Jennifer Guergues Guergues Mar 2019

Advanced Proteomic And Epigenetic Characterization Of Ethanol-Induced Microglial Activation, Jennifer Guergues Guergues

Graduate Theses and Dissertations

Microglia, the resident immune cells of the brain, can exhibit a broad range of activation phenotypes and have been implicated in several diseases and disorders of the central nervous system. Here, we described a method optimized for sensitive and rapid quantitative proteomic analysis of microglia that involves suspension trapping (S-Trap) for efficient and reproducible protein extraction from a microglial cell count expected from an individual mouse brain (~300K) while also simultaneously providing the first comprehensive proteomic characterization of a novel adult-derived mouse microglial cell line. This enhanced method was used throughout all subsequent works and was especially necessary when we ...


Investigating The Role Of The Chromosome 19 Microrna Cluster In Human Trophoblast Differentiation And Infantile Hemangioma, Ezinne Francess Mong Mar 2019

Investigating The Role Of The Chromosome 19 Microrna Cluster In Human Trophoblast Differentiation And Infantile Hemangioma, Ezinne Francess Mong

Graduate Theses and Dissertations

Trophoblast differentiation and invasion is essential for normal implantation and establishment of the maternal-fetal interface, which allows for proper nutrient exchange and support of the fetus. For this to occur, cytotrophoblasts must undergo an epithelial to mesenchymal transition and differentiate into migratory and invasive extravillous trophoblasts (EVTs) that invade the maternal decidua and myometrium. Trophoblast differentiation, migration and invasion is highly regulated by a complex network of signaling pathways, adhesion molecules and transcription factors and is important for the remodeling of maternal spiral arteries from low flow, high resistance to high flow, low resistance vessels to allow optimal perfusion of ...


Conserved Glycine Residues Control Transient Helicity And Disorder In The Cold Regulated Protein, Cor15a, Oluwakemi Sowemimo Mar 2019

Conserved Glycine Residues Control Transient Helicity And Disorder In The Cold Regulated Protein, Cor15a, Oluwakemi Sowemimo

Graduate Theses and Dissertations

COR15A is a cold regulated disordered protein from Arabidopsis thaliana that contributes to freezing tolerance in plants by protecting membranes. It belongs to the (LEA) Late Embryogenesis Abundant group of proteins that accumulate during the later stage of seed development and are expressed in various parts of the plant. During freezing-induced cellular dehydration, COR15A transitions from a disordered structure to a mostly α-helical structure that binds and stabilizes chloroplast membranes when cells dehydrate due to freezing. We hypothesize that increasing the transient α-helicity of COR15A under normal conditions will increase its ability to bind and protect chloroplast membranes when cells ...


Biochemical And Proteomic Approaches To Determine The Impact Level Of Each Step Of The Supply Chain On Tomato Fruit Quality, Robert T. Madden Mar 2019

Biochemical And Proteomic Approaches To Determine The Impact Level Of Each Step Of The Supply Chain On Tomato Fruit Quality, Robert T. Madden

Graduate Theses and Dissertations

Fresh fruits and vegetables (FFVs) are the most frequently wasted foods because of their perishability and handling requirements. However, there is a lack of information on how much each step of the supply chain impacts FFVs quality, particularly on tomatoes, and what measures need to be taken for an immediate and effective impact on waste reduction. There is also no information on how the supply chain affects the proteome of the tomato and what proteins are differentially regulated by the most impactful steps of the supply chain. The objectives of the work presented on this thesis were to evaluate the ...


Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone Mar 2019

Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone

Graduate Theses and Dissertations

This dissertation covers a variety of the genetic and molecular abnormalities of lung adenocarcinoma with an emphasis on STK11 loss and its implications on immunotherapy response. Given that lung cancer is the leading cancer killer, novel therapies are in great demand. In particular, immunotherapy has shown some of the most promise in the last decade but remains limited due to nearly 80% of patients not significantly responding. This dissertation aims to molecularly characterize lung adenocarcinoma while attempting to explain the reason why patients with STK11 loss do not respond to immunotherapy.

In the first chapter we discuss the relationship between ...


Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher Jan 2019

Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher

Graduate Theses and Dissertations

Swine with severe combined immunodeficiency (SCID) are an emerging large animal model for biomedical research. There have been several SCID pig models described since our first discovery of naturally occurring SCID with mutations in Artemis (DCLRE1C) in 2012. SCID animals are particularly useful in biomedical research due to their lack of T, B, and sometimes NK cells. Absence of the adaptive immune system allows for human cell and tissue xenotransplantation into these SCID animals. The works described within this thesis are categorized under four main goals: (1) further characterization of the immune system of Art-/- SCID pigs, (2) development of ...


Ectopic Expression Of The Arabidopsis Homomeric Acetyl-Coa Carboxylase, Troy Matthew Bunch Jan 2019

Ectopic Expression Of The Arabidopsis Homomeric Acetyl-Coa Carboxylase, Troy Matthew Bunch

Graduate Theses and Dissertations

A number of economic and environmental imperatives have spurred an increased demand for biologically sourced, chemically reduced forms of carbon. Fatty acids, and closely related derivatives, represent an abundant form of such biological carbon. The biosynthesis of these molecules requires acetyl-CoA as a primer substrate, and malonyl-CoA as the extender substrate. Malonyl-CoA is generated by the carboxylation of acetyl-CoA, a reaction catalyzed by acetyl-CoA carboxylase (ACCase), which is thought to be an important determinant of the rate limiting reaction of fatty acid biosynthesis. In Arabidopsis, as in most dicotyledonous plants, two distinct isozymes catalyze this reaction, a cytosolic homomeric form ...


Epigenetic Variation In A Reptile With Temperature-Dependent Sex Determination And Inspiring A Diverse Future For Stem, Daniela Victoria Flores Jan 2019

Epigenetic Variation In A Reptile With Temperature-Dependent Sex Determination And Inspiring A Diverse Future For Stem, Daniela Victoria Flores

Graduate Theses and Dissertations

Vertebrates with temperature-dependent sex determination (TSD), a mechanism that relies on incubation temperature to irreversibly determine the sex of developing embryos, are threatened by ongoing changes in climate and local environmental conditions. Previous studies have suggested that behavioral and molecular plasticity in this system may provide opportunities for these species to adapt to these changes. Although decades of research have uncovered key aspects, a complete molecular mechanism of TSD remains elusive. Epigenetic studies have the potential to unlock crucial information previously cryptic in traditional genetic studies. Recent studies have shown that environmental factors and maternal effects can greatly influence an ...


Stimulation Of Pgc-1Α To Attenuate Duchenne Muscular Dystrophy Disease Pathology And Activate Autophagy, Hannah Spaulding Jan 2019

Stimulation Of Pgc-1Α To Attenuate Duchenne Muscular Dystrophy Disease Pathology And Activate Autophagy, Hannah Spaulding

Graduate Theses and Dissertations

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by the absence of functional dystrophin protein. Dystrophin-deficiency results in numerous cellular dysfunctions and increased muscle injury leading to progressive muscle weakness and ultimately death due to cardiomyopathy or respiratory insufficiency. Overexpression of the transcriptional coactivator, PGC-1α, has been shown to provide therapeutic benefits for dystrophic muscle. In a preliminary experiment, quercetin, a nutraceutical that can drive PGC-1α through SIRT1, protected dystrophin-deficient skeletal muscle following 6 months of treatment. Therapies for DMD must demonstrate long-term efficacy, therefore in the first research chapter we evaluated the effect of 12 months ...


Characterization Of Lamp1 In Drosophila Melanogaster, Norin Yasin Chaudhry Jan 2019

Characterization Of Lamp1 In Drosophila Melanogaster, Norin Yasin Chaudhry

Graduate Theses and Dissertations

Lysosome Associated Membrane Proteins (LAMPs) are the most abundant proteins in the lysosomal membrane and are important for maintaining the structural integrity of the lysosomes and separating the hydrolytic enzymes inside the lysosomal lumen from the cell cytoplasm. Additional functions of Lamp proteins are continued to be discovered and they have been recently characterized for their involvement in autophagy in different mammalian systems. LAMP-1 and LAMP-2 are ubiquitously expressed in mammals. LAMP-2 has 3 splice variants and mutations in LAMP-2B have been shown to cause Danon disease in humans, characterized by the accumulation of autophagic vacuoles in the heart and ...


Biomarkers Of Insulin Resistance, Oxidative Stress, And Nutrition And The Brain, Kelsey Elizabeth Mclimans Jan 2019

Biomarkers Of Insulin Resistance, Oxidative Stress, And Nutrition And The Brain, Kelsey Elizabeth Mclimans

Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a neurological disorder that has been linked with nutrition and lifestyle choices throughout the lifespan. Although there is currently no cure, recent research supports dietary changes as a preventative measure for AD. However, it is not clear which nutritional markers underlie the structural and functional changes in the brain that are seen in AD, and subsequently what aspect of the diet should be targeted in AD prevention and treatment. The projects described in this dissertation provide four nutritional biomarkers that are associated with AD pathology: the metabolism-regulating enzyme autotaxin, the insulin transporter and modifier insulin-like ...


Analysis And Characterization Of The Choline-Utilizing Microcompartment In Uropathogenic E. Coli 536, Taylor Irene Herring Jan 2019

Analysis And Characterization Of The Choline-Utilizing Microcompartment In Uropathogenic E. Coli 536, Taylor Irene Herring

Graduate Theses and Dissertations

Bacterial microcompartments (MCPs) are subcellular organelles that are widespread among bacteria. MCPs consist of metabolic enzymes encapsulated within a protein shell and their function is to increase the efficiency of metabolic processes in part by sequestering toxic and volatile intermediates. MCPs are found in about 20% of bacteria. In several cases, MCP production is correlated to bacterial pathogenesis. In addition, because of their metabolic role in the human gut microbiome, MCPs are linked to cancer and heart disease. Only three of ten MCP types have been well-studied. Recently, a new type of MCP that is used to metabolize choline under ...


Discovery And Sequencing Of Novel And Identified Mosquito-Associated Viruses And Genetic Determinants Of Flavivirus Host Specificity, Jermilia Charles Jan 2019

Discovery And Sequencing Of Novel And Identified Mosquito-Associated Viruses And Genetic Determinants Of Flavivirus Host Specificity, Jermilia Charles

Graduate Theses and Dissertations

The advent of globalization and the continuing effects of climate change have exposed an even greater percentage of the world to disease agents carried by vectors which were once thought to be restricted to tropical or subtropical areas. Arthropods vectors such as mosquitoes and ticks harbor a number of emerging and re-emerging pathogens of public and veterinary health importance worldwide. These pathogens include viruses from four major families including the Flaviviridae, Bunyaviridae, Togaviridae and Reoviridae families. The Flavivirus genus is one of four genera in the Flaviviridae family, with over 70 species, the great majority of which are maintained in ...