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Tumor-Targeted Conjugated Polymer Nanoparticles With Encapsulated Iron And Its Biomedical Application For In Vitro Killing Of Melanoma Cell Lines Through Ferroptosis Assisted Chemodynamic Therapy (Cdt), Khalaf Jasim

Electronic Theses and Dissertations

Melanoma represents one of the most aggressive and lethal forms of skin cancer, with annually rising incidences throughout the world. Although chemotherapy modalities remain the mainstay of treatment, the therapeutic potential of chemotherapy typically is hampered by multidrug resistance (MDR) and nonspecific drug distribution that causes side-effects. To surmount such limitations, novel nanoformulations of low band-gap poly ({4,8-bis [(2-ethylhexyl) oxy] benzo [1,2-b:4,5-b?] dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl) carbonyl] thieno [3,4-b] thiophenediyl}) (PTB7) and poly [2,1,3-benzothiadiazole- 4,7- diyl [4,4-bis (2-ethylhexyl)- 4H-cyclopenta [2,1-b:3,4-b'] dithiophene-2,6-diyl]] (PCPDTBT) were fabricated by a reprecipitation method. These conjugated polymer nanoparticles were functionalized with the polypeptide endothelin-3 (EDN3-CPNPs) to target melanoma. The …

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle repression by …

Studies Of Oxidative Damage, Brain Proteome, And Neurochemical Metabolites In Cognitive And Neurodegenerative Disorders: (1) Chemotherapy-Induced Cognitive Impairment; (2) Parkinson Disease Rat Model, Xiaojia Ren

Theses and Dissertations--Chemistry

The rate of cancer patients is increasing as the development of science and technology. Twenty million cancer survivors are estimated living in the United States by 2025. However, many cancer survivors show cognitive dysfunction, negatively affecting the quality of life. These cognitive impairments are recognized as chemotherapy-induced cognitive impairment (CICI), also called "chemo brain" by cancer survivors, including the diminished ability of memory and learning, hard to concentrate and focus, as well as diminution of executive function and processing speed. The etiologies and pathologies of CICI are complicated, especially in most cases the anti-cancer drug cannot cross the blood-brain barrier …

Investigation Of Amyloid Β Oligomer Dissociation Mechanisms By Single Molecule Fluorescence Techniques, Hope Cook Abdalla

Theses and Dissertations--Chemistry

Alzheimer’s disease (AD) is currently considered the most prevalent neurodegenerative disease and places a large financial burden on society as healthcare resources are limited and the disease does not have a cure. Alzheimer’s disease is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles; however current literature suggests Aβ oligomers are the main aggregating species leading to AD symptoms. Therefore, the underlying cause of Alzheimer’s, accumulation of amyloid beta, is currently being studied in hopes of developing treatment options. Our research aims at determining the mechanism and kinetics of Aβ oligomer dissociation into non-toxic monomers in the …

The Role Of Rmta In The Opportunistic Pathaogen Aspergillus Fumigatus, Roshan Dahal

Graduate Research Theses & Dissertations

The fungus Aspergillus fumigatus is an opportunistic human pathogen capable of causing

a life-threatening systemic lung infection known as invasive aspergillosis among immune compromised

patients. This group includes individuals infected with HIV, people with hematological

malignancies, solid organ transplant patients, persons with genetic immunodeficiency and cancer

patient undergoing chemotherapy. Due to the medical relevance of this organism, it is imperative

to discover novel genetic elements to design antifungal drugs against A. fumigatus dissemination,

virulence and survival during human infection. Previously, the putative arginine methyltransferase

gene rmtA was characterized in the model organism Aspergillus nidulans and the opportunistic

plant pathogen Aspergillus …

Hif-2 Regulation Of Amino Acid Transporter Expression In Hepatocellular Carcinoma Cells, Jason A. Misurelli

Graduate Research Theses & Dissertations

Hypoxia represents a major driver of the cancer phenotype in solid tumors, especially those of hepatic origin. Low oxygen availability triggers a complex cellular response which alters metabolism and promotes cellular invasion. Growing evidence suggests the amino acid glutamine, an important molecular currency for both energy producing reactions and biosynthetic pathways, plays an enhanced role in cancer cells under hypoxia. Hypoxia-inducible factors (HIFs) are transcription factors crucial for regulating the cellular response to low oxygen. Family member HIF-1 has been well studied, however, recent evidence suggests HIF-2 may have a regulatory role in amino acid transport and metabolism under hypoxia. …

Impact Of Conformational Change, Solvation Environment, And Post-Translational Modification On Desulfurization Enzyme 2'-Hydroxybiphenyl-2-Sulfinate Desulfinase (Dszb) Stability And Activity, Landon C. Mills

Theses and Dissertations--Chemical and Materials Engineering

Naturally occurring enzymatic pathways enable highly specific, rapid thiophenic sulfur cleavage occurring at ambient temperature and pressure, which may be harnessed for the desulfurization of petroleum-based fuel. One pathway found in bacteria is a four-step catabolic pathway (the 4S pathway) converting dibenzothiophene (DBT), a common crude oil contaminant, into 2-hydroxybiphenyl (HBP) without disrupting the carbon-carbon bonds. 2’-Hydroxybiphenyl-2-sulfinate desulfinase (DszB), the rate-limiting enzyme in the enzyme cascade, is capable of selectively cleaving carbon-sulfur bonds. Accordingly, understanding the molecular mechanisms of DszB activity may enable development of the cascade as industrial biotechnology. Based on crystallographic evidence, we hypothesized that DszB …

Illuminating Dna Packaging In Sperm Chromatin: How Polycation Lengths, Underprotamination And Disulfide Linkages Alters Dna Condensation And Stability, Daniel Kirchhoff

Theses and Dissertations--Chemistry

During spermiogenesis, somatic chromatin is remodeled and a vast majority (> 90%) of DNA histones are replaced by short arginine-rich peptides called protamines. This compaction is immense, with protamine-DNA self-assembly in sperm chromatin resulting in a final volume roughly 1/6th of a somatic nucleus. This near crystalline organization of the DNA in sperm is thought crucial both for the transport of the paternal genes as well as for the protection of genetic information as sperm chromatin is transcriptionally inactive and all DNA repair mechanisms are shut down.

Chapter 1 will include an overview of the topics discussed in this document, …

Detection Of Beta-Lactamase Variants In Municipal Wastewater And Fresh Water, Sunil Pandey

Masters Theses

The occurrence and spread of antibiotic-resistant genes (ARGs) are pressing public health problems worldwide. A key factor contributing to the spread of ARGs is lateral gene transfer. Wastewater treatment plants (WWTPs) are measured hot spots of microbial diversity and resistance because they receive polluted wastewater from diverse sources and contain a variety of different environments with dense bacterial loads. Due to the overuse of antibiotics the genetic capacities of microbes have profited. This helps every source of resistance gene and every means of horizontal gene transmission to develop the multiple mechanism of resistance to each antibiotic used clinically, agriculturally, or …

Functions Of Dfrp And Other Drg Pathway Genes In The Moss Physcomitrella Patens, Robert James Srygler

Graduate Research Theses & Dissertations

GTP binding proteins (G proteins) are molecular switches that regulate many aspects of physiology in all cells. DRG1 and DRG2 (Developmentally Regulated GTP-binding proteins) have been found in all eukaryotes examined. Amino acid identity across eukaryotes is about 65% within an orthologous group and 55% between paralogs of a single species. Although DRGs are likely involved in some aspect of translation regulation, details of their precise cellular functions are not known.

In addition to DRGs there are other genes/proteins that comprise the “DRG pathway.” DFRPs (DRG Family Regulatory Proteins) have been shown to physically and genetically interact with DRGs. Previous …

Multi-Scale Computational Studies Of Calcium (Ca2+) Signaling, Bin Sun

Theses and Dissertations--Chemistry

Ca²⁺ is an important messenger that affects almost all cellular processes. Ca²⁺ signaling involves events that happen at various time-scales such as Ca²⁺ diffusion, trans-membrane Ca²⁺ transport and Ca²⁺-mediated protein-protein interactions. In this work, we utilized multi-scale computational methods to quantitatively characterize Ca²⁺ diffusion efficiency, Ca²⁺ binding thermodynamics and molecular bases of Ca²⁺-dependent protein-protein interaction. Specifically, we studied 1) the electrokinetic transport of Ca²⁺ in confined sub-µm geometry with complicated surfacial properties. We characterized the effective diffusion constant of Ca²⁺ in a cell-like environment, which helps to understand …

Xylan Metabolism By Caulobacter Crescentus, Viet Bui

Masters Theses

Bacteria present unique opportunities to explore the molecular mechanisms of nutrient acquisition processes at single cell level under various experimental conditions. Caulobacter crescentus is a gram-negative oligotrophic environmental bacterium with adaptive physiological responses, such as slow growth or complete arrest of cell cycle, presence of sessile and motile progenies with the sessile cells growing stalk to enhance nutrient uptake for growth in low-nutrient conditions. Details of plant polysaccharide-derived carbon compound, such as cellobiose, maltose, and xylose utilization by C. crescentus can be found but molecular details or mechanisms of polysaccharide utilization, such as xylan, has not been reported. Database analyses …

Measuring The Impact Of Oesophagectomy On Physical Functioning And Physical Activity Participation: A Prospective Study, E.M. Guinan, A.E. Bennett, Suzanne Doyle, Luke O'Neill, J. Gannon, G. Foley, J.A. Elliott, J. O'Sullivan, J.V. Reynolds, J. Hussey

Articles

Background: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from presurgery through 6-months post-oesophagectomy. Methods: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured presurgery (T0) …

Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit

Master's Theses

Hepatic steatosis (fatty liver) is increasingly prevalent in the US, and is characterized by triglyceride accumulation within hepatocytes. This is a direct result of an imbalance between lipid import, export, de novo lipogenesis, and beta oxidation. Hepatic steatosis can also progress to nonalcoholic steatohepatitis (NASH) which is characterized by increased hepatocyte damage, inflammation, and fibrosis. Further progression can lead to liver failure or hepatocellular carcinoma, requiring liver transplant or causing death. Our lab recently created Mllt3 conditional whole body knockout mice. These mice developed hepatic steatosis and NASH following Mllt3 deletion. MLLT3 is a master gene regulator that is part …

Structural Characterization Of Black Widow Spider Dragline Silk Proteins Crp1 And Crp4, Mikayla Shanafelt

University of the Pacific Theses and Dissertations

Spider dragline silk is a biomaterial with outstanding material properties, possessing high-tensile strength and toughness. In nature, dragline silk serves a central role during spider locomotion and web construction. Today, scientists are racing to elucidate the molecular machinery governing silk extrusion, attempting to translate this knowledge into a mimicry process in the laboratory to create synthetic fibers for a wide range of different applications. During extrusion, it has been established that biochemical and mechanical forces govern spidroin folding, aggregation, and assembly. In black widow spiders, at least 7 different proteins have been identified as constituents of dragline silk fibers. These …

Development Of A Biomarker Panel For Identifying Stressed Marine Mammals, Laura Pujade

University of the Pacific Theses and Dissertations

Increasing anthropogenic disturbance in marine ecosystems such as fishing, oil-drilling, and noise pollution can have detrimental effects on the reproduction and survival of apex predators such as marine mammals. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased circulating glucocorticoid (GCs) hormones, which alter expression of target genes encoding metabolic enzymes and other mediators of stress. Prolonged HPA axis stimulation may increase catabolism of nutrient stores and suppress immune and reproductive functions, impacting the fitness of marine mammals. GCs measurements are used to identify wild animals experiencing stress. However, these measurements may not be sensitive enough to distinguish between an …

Evaluating Methods Of Obtaining Male Pheromone From Hymenochirus Sp. Using Analytical Chemistry, Vincent Wing-Kun Leung

University of the Pacific Theses and Dissertations

Male Hymenochirus sp. frogs are known to release pheromone that attracts females of the same species. Four methods for collecting secretions containing pheromone in Hymenochirus sp. were tested: norepinephrine injection, gonadotropin-releasing hormone injection, homogenization of gland tissue, and electrostimulation of the skin over the breeding gland area. The samples collected were analyzed using high-performance liquid chromatography (HPLC) and mass spectrometry. The HPLC chromatograph for the male norepinephrine sample contained a peak at 6.4 min that was not in the female norepinephrine sample HPLC chromatograph. The male norepinephrine sample mass spectrum had a peak of m/z 292.0 not in the female …

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …

Assessing The Effects Of Antioxidants On Oxidative Stress In Triple-Negative Breast Cancer Cells Via Protein Carbonylation, Dalton Sheffield

Honors Theses

Breast cancer is a highly complex, heterogeneous disease, and potential effective treatment options are being continuously researched in order to provide a method of halting cancer growth and metastasis. One area in particular involves alleviating oxidative stress within cancer cells. Oxidative stress is generally defined as an imbalance between oxidant and antioxidant species in favor of the oxidants. Cancer cells use this oxidative stress to initiate carcinogenesis in cells through different mechanisms, and protein carbonylation is a primary biomarker used to quantify oxidative stress levels. Antioxidant compounds are those used to alleviate oxidative stress within cells. Here breast cancer cells …

Protein Templated Silver Nanoclusters, Greyson Keel

Honors Theses

Nanoclusters are smaller than their nanoparticle counterparts and have unique properties. Most research has been done on gold nanoclusters, but silver nanoclusters are said to be more robust. During the process of trying to create nanoclusters, several methods in the procedure were changed when gathering data: determining a successful silver concentration, working with the correct buffer, mixing gold and silver metals together, observing the effects of pH, and finding a good reducing agent. After experimenting with those changes, a successful protocol was adapted and modified from literature (Journal of Materials Chemistry, 2011, 21, 11205-11212) to produce the protein-templated Ag clusters. …

Benchmark Structures And Harmonic Vibrational Frequencies Of Hydrated Halide Ions: X– (H2o)N, X = F, Cl, Br, And I (Where N = 1 – 4), Caroline Anne Rader

Honors Theses

This study extends our efforts to generate benchmark structures and harmonic vi- brational frequencies from neutral hydrogen bonded clusters to solvated ions. The analytical gradients and Hessians developed for the N-body:Many-body integrated QM:QM method facilitate the computation of benchmark-quality properties near the CCSD(T) complete basis set limit. In this work, a series of solvated halide ion sys- tems (X−(H2O)n clusters, where X = F, Cl, Br and I and n = 1 to 4) is being characterized with the MP2 and 2-body:Many-body CCSD(T):MP2 (2b:Mb) meth- ods. For n ≥ 2, the latter technique uses the high-level CCSD(T) method to evaluate …

Time- And Ph- Dependent Proteolysis Of Engineered Proteins By Collagenase, Hunter Berry

Honors Theses

Pleiotropic effects from oral administration of anti-inflammatory drugs limit their effectiveness. The ultimate goal of this project is to develop a novel self-assembling protein-based hydrogel for in situ delivery of NSAIDs at the site of chronic inflammation. Since inflammation causes acidification and activation of collagenases in the inflamed tissue, we have designed the hydrogel to respond to both of these queues to effectively deliver drug at the site. Self-assembly of the protein hydrogel exploits the high affinity and specific interaction between the protein calmodulin (CaM) and its specific binding peptide, M13. The two components of the hydrogel, CCLP and PCLP …

Lost In Translation: Challenges And Solutions To Language Barriers In Healthcare In Mississippi, Galina Ostrovsky

Honors Theses

Language barriers can impede access to healthcare and compromise quality of care for limited English proficiency (LEP) patients. Although a rights-based framework would suggest and federal mandates require healthcare facilities to provide language access services, multiple factors result in the persistence of language barriers in healthcare. As the literature review shows, these factors include limitations in policy, enforcement, standardization, resources, and ability to recruit and retain professional interpreters. This thesis uses a multi-method case study entailing Mississippi in general and information from two specific sites, a rural Delta county and an urban central county, to assess the issue of language …

Characterization Of The Effects Of Sex And Estrogen Receptor Signaling On Antigen-Specific T Cells For Immunotherapy, Flor Cecilia Navarro Negredo

Dissertations

Adoptive cell transfer (ACT) immunotherapy using antigen (Ag)-specific T cells is partially effective treating several malignancies but numerous challenges remain in order to improve its therapeutic potential. The roles of host factors, such as sex hormone receptor signaling, that can affect the T cell anti-tumor function remain understudied. The work performed in this dissertation characterized the role of estrogen signaling on T cell function in vitro, and during ACT immunotherapy against hepatocellular carcinoma (HCC) in vivo. Estrogen signaling through ERa enhanced the expression and secretion of Type I effector cytokines including IFNg, TNFa, and Granzyme B in male and female …

Yczr, A New Case Of Plp-Dependent Mocr/Gabr Type Transcription Regulator In Klebsiella Pneumonia, Yuanzhang Zheng

Dissertations

Increasing number of genes encoding PLP-dependent transcription regulators, MocR/GabR type regulators, have been identified in various bacterial genomes. However, only a handful of them, including MocR, PdxR and GabR have been studied experimentally. They control different aspects of the bacterial metabolism. Only GabR has reported crystallographic structures. MocR/GabR regulators possess a chimeric structure consisted of a WHTH DNA binding domain and an Aminotransferase-like regulation domain, which can bind PLP as an effector in transcription regulation. Such a chimeric construct presents an interesting case in molecular evolution. The regulation domains of All MocR/GabR type regulators loss their catalytic capacity during evolution …

Co-Expression Of Feedback Resistant Enzymes In Phenylalanine Biosynthesis Pathway To Increase Phenylalanine Production, Charintip Yenyuvadee

Chulalongkorn University Theses and Dissertations (Chula ETD)

L-Phenylalanine (L-Phe) is an important commercial amino acid. It is widely used in food and pharmaceutical industries. Currently, the requirement of L-Phe is increased according to the great demand for the low-calorie sweetener, aspartame. In Escherichia coli, the synthesis of L-Phe is controlled by the multi-hierarchical regulations. AroG isoform of 3-deoxy- D-arabino-heptulosonate-7-phosphate synthase (DAHP synthase) and chorismate mutase/prephenate dehydratase (PheA), two important enzymes, are feedback inhibited by LPhe. Co-expression of feedback-resistant pheA (pheA[superscript L359D]) with other pivotal genes in L-Phe biosynthesis pathway: aroB, aroL, phedh, tktA, aroG, pheA, yddG, and glpF in pRSFDuet-1 (pPTFBLYA[superscript L359D]) elevated L-Phe production of E. …

Functional Characterization Of Cytosolic Ddx41 Sensor In Mediating Antiviral Immune Response In Black Tiger Shrimp Penaeus Monodon, Suthinee Soponpong

Chulalongkorn University Theses and Dissertations (Chula ETD)

DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), a receptor belonging to the DExD family, was recently identified as an intracellular DNA sensor in vertebrates. Here, we investigated the presence of cytosolic DNA sensing, DDX41 in shrimp Penaeus monodon. By searching for gene involved in DNA sensing cascade within the shrimp P. monodon EST database, 3 cDNA fragments exhibited similarity to DDX41 in various species were identified. Sequences assembly resulted in a complete ORF of Penaeus monodon DDX41 (PmDDX41) which has 1868-bp encoding a putative protein of 620 amino acid residues. The multiple sequence alignment of deduced amino acid sequence of PmDDX41 …

Fructooligosaccharide Synthesis By Immobilized Inulosucrase From Lactobacillus Reuteri 121 And Improvement Of Product Pattern Using Site-Directed Mutagenesis, Thanapon Charoenwongpaiboon

Chulalongkorn University Theses and Dissertations (Chula ETD)

Inulin-type fructooligosaccharides (IFOS) are well-known prebiotics which can be produced from sucrose using bacterial inulosucrase (E.C. 2.4.1.9). However, the use of inulosucrase for IFOS synthesis has some limitations because it also synthesizes some polysaccharides and exhibits lower stability than the fungal enzymes. To overcome these limitations, improvement of inulosucrase was made by using enzyme immobilization and enzyme engineering. First, inulosucrase from Lactobacillus reuteri 121 was immobilized on a novel, high capacity core-shell chitosan beads using glutaraldehyde as a cross-linker. The results showed that both immobilized and free inulosucrase had the same optimum pH (5.5), while the optimum temperature was shifted …

Development Of Paper-Based 3d Cell Culture Devices And Real-Time Biosensing Applications, Naricha Pupinyo

Chulalongkorn University Theses and Dissertations (Chula ETD)

Due to its micro fibrous pores, paper has gained traction in the use as a scaffold for 3D cell culture. To study melanoma mechanism, screening the amount of melanin production and invasion study are major keys for drug development. In this work, we developed paper-based devices for culturing melanoma cells. Through the development process, we obtained the optimal parameters, which were applied for 3 different projects; 1) Anti-melanogenic effect screening, 2) Impedance-based E-screen assay, and 3) A membrane insert for real-time invasion assay. As a result of melanin production from melanocytes, the cells can be easily observed after a few …

Effects And Mechanisms Of Caesalpinia Mimosoides Leaf Extract On Oxidative Stress Resistance And Anti-Aging Activity In Caenorhabditis Elegans And Neurite Outgrowth Activity In Neuro2a Cells, Panthakarn Rangsinth

Chulalongkorn University Theses and Dissertations (Chula ETD)

World’s population of older people is rising, dietary supplements promoting healthy lifespan are needed. Moreover, Alzheimer’s disease (AD), an age-related degenerative disease, becomes a public health problem in aging society. Recent reports using cell culture models of AD suggest that amyloid precursor protein (APP), a protein causally related to AD, plays an important role as an inhibitor of neurite outgrowth. Medicinal herbs with neurite outgrowth stimulatory effect may help to prevent and cure AD. Moreover, studies suggest that dietary supplements from plant sources act in preventive nutrition, since they provide antioxidant action against oxidative stress, promote healthspan and prolong lifespan. …