Life Sciences Commons^™

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

Neuromuscular Development And Phenotypic Variation In Zebrafish Models Of Dystroglycanopathy, Erin Bailey

Electronic Theses and Dissertations

Skeletal muscle is highly conserved among vertebrates and is essential for strength and locomotion. This tissue becomes integrated with the skeletal system via tendons at the myotendinous junction and with the nervous system at the neuromuscular junction. Both of these specialized junctions are rich in extracellular matrix, a protein scaffold that occupies the extracellular space of cells. Skeletal muscle is also highly plastic and can grow in size (hypertrophy) or lose mass (atrophy) in response to genetic or environmental cues. Muscle atrophy is found in individuals battling a number of neuromuscular conditions, including muscular dystrophy. Muscular dystrophies are a suite …

The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui

Electronic Theses and Dissertations

Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins α_Dβ₂ and α_Mβ₂ to macrophage migration and development of chronic inflammation.

We found that integrin α_Dβ₂ is upregulated on M1-macrophages in vitro and …

Characterization Of A More Clinically Relevant Human Leukemia Xenograft Model To Examine Perturbation Of Met/Sam Metabolism As A Novel Therapeutic Paradigm For Mll-R Leukemia In Vivo., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML), is a heterogeneous clonal disorder characterized by an accumulation of malignant myeloid progenitors in the bone marrow (BM), hindering normal hematopoiesis. AML exhibits dramatic heterogeneity in terms of cytogenetics, morphology, and chemotherapeutic sensitivity. Therefore, the investigation of novel, efficacious AML therapeutics will require advanced preclinical in vivo model systems, capable of recapitulating patient specific disease heterogeneity, and induction chemotherapy outcomes. A major focus and eventual outcome of this work was the establishment and development of a more clinically relevant mouse xenograft model of patient AML, that efficiently harbors patient derived xenografts (PDXs), and unlike more prevalent …

Muscle Degeneration In A Zebrafish Model Of Lysosomal Related Myopathy, Elizabeth Coffey

Electronic Theses and Dissertations

Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth and homeostasis is modulation of protein turnover. Protein turnover is the balance between synthesis and degradation of muscle proteins. The rate of protein degradation is the major factor underlying overall muscle growth during development. Protein degradation mainly takes place in the lysosome. The efficiency of lysosomal protein degradation depends upon lysosomal pH, which is generated and maintained by proton pumps. Despite the importance of protein degradation in muscle growth during development, the impact of dysregulated lysosomal pH on muscle development, growth, …

Exploring The Role Of Ptn1 In Ustilago Maydis., Lalu Murali Krishna Vijayakrishna Pillai

Electronic Theses and Dissertations

Signal transduction is a key aspect of biological life. Cell signaling involves a series of biochemical and molecular steps that regulate the normal cellular functions, and any disruption at any of these steps is likely to have substantial impacts on cell physiology. The current study was aimed at the characterization of ptn1 of Ustilago maydis, a basidiomycete fungus. When the U. maydis, ptn1 gene was either deleted or overexpressed, it was found that the deletion of this gene lead to reduced virulence, spore production, and germination rate; effects of the overexpression were more subtle or not discernable. Previous studies …

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

Identifying Critical Genes For Cholesterol Metabolism In Macrophages Using Crispr-Cas9 Whole-Genome Screens, Kevin Wanniarachchi

Electronic Theses and Dissertations

Macrophage foam cells contribute to atherosclerotic plaque formation, a pathology that underlies heart disease, peripheral arterial disease and stroke. Foam cells form when macrophages take up excessive amounts of low-density lipoprotein (LDL) leading to elevated cellular levels of neutral lipids, which are packaged into lipid droplet organelles. Despite the high public health priority motivating research of cardiovascular disease processes, current understanding of macrophage cholesterol metabolism including mechanisms of LDL uptake, cholesterol trafficking, lipid droplet biogenesis, lipid droplet degradation and cholesterol efflux is limited. Here, we implemented a CRISPR-Cas9 whole genome screening strategy to identify critical genes regulating macrophage cholesterol metabolism. …

Investigation Of Intergroup Bias In Two Neuromaturationally Distinct Age Cohorts: An Erp Study, Reuven M. Hanna

Electronic Theses and Dissertations

Currently, sociological investigation of adolescent behavior focuses on the intersection of biography, history, and structure to explain adolescent risk-taking, reward-seeking, impulsivity, novelty-seeking and peer-salience. However, the preponderance of the evidence points away from social ecology and to a significant neuromaturational restructuring event between the 12th and 25th years of life as the root of adolescent behavioral tendencies. As a result, sociological social psychology can benefit from engaging in basic research using neuroscience methods. The present study expands the dual systems model of brain development to account for maturational changes in the social brain network as a way to explain social …

Transgenerational Effects Of Maternal Age On Offspring Fitness In Crickets, Jacob D. Wilson

Electronic Theses and Dissertations

Advanced parental age is an important aspect of parental condition that can have both positive and negative effects on offspring fitness, and thus, parental age can be considered a parental effect. As a parental effect, parental age may affect a variety of offspring traits and may cascade to influence several generations of offspring. Given the complexities of studying both paternal and maternal age, we studied the effects of maternal age only. Using the Pacific field cricket, Teleogryllus oceanicus, we asked 1) does maternal age have influences over several generations of offspring and 2) does maternal age influence the reproductive …

New Insights Into Mycofactocin Biosynthesis, Structure And Function, Richard Selorm Ayikpoe

Electronic Theses and Dissertations

Mycofactocin is a putative ribosomally synthesized and post-translationally modified peptide (RiPP)-derived redox cofactor. Its biosynthesis is accomplished through the dedicated actions of the products of six conserved genes, mftABCDEF. The mycofactocin pathway is one of the most widely distributed RiPP systems in bacteria however, this distribution is heavily skewed towards the Mycobacteria genus including human pathogenic variants such as M. tuberculosis and M. ulcerans. Gene expression studies have demonstrated the essentiality of the pathway in the ability of M. tuberculosis to utilize the host's cholesterol as sole carbon source during latency. However, the biosynthesis, structure and physiological function …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

Electronic Theses and Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …