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Novel Photobase Generators For Photoinduced Polymerization And Ph Regulation, Shupei Yu

Dissertations

Photochemistry encompasses the investigation of chemical processes instigated by light absorption. As important branches of photochemistry, photosensitive and optical materials have attracted extensive research interests in both academia and industry. Photosensitive and optical materials are composed of polymers / small molecules with photo-responsive properties. These materials not only can absorb light in the desired energy spectrum, but also exhibit chemical / physical reactions, which can be applied to different fields such as photoredox, photo-heat, phototherapy, solar cells, diodes, etc. Among them, photobase generators (PBGs) are a series of photosensitive compounds, which absorb the incident light, then release the basic species …

Biophysical Factors Affecting Habitat Suitability For Crassostrea Virginica, Jason D. Tilley

Dissertations

Oyster reefs provide a variety of important ecosystem services. However, the mortality rate of eastern oyster, Crassostrea virginica, the dominant species that produces oyster reefs in the northern Gulf of Mexico, is increasing at an alarming rate due to a variety of abiotic and biological factors. I examined how biophysical factors, including the less-studied fatty acid profiles of the suspended particulate matter on which oysters feed, influenced morphometric condition of C. virginica.

I sampled suspended particulate matter (SPM) and oysters in-situ in the western Mississippi Sound, which historically supported the majority of oyster production in Mississippi waters. Sampling …

Binding Interactions Of Biologically Relevant Molecules Studied Using Surface-Modified And Nanostructured Surfaces, Palak Sondhi

Dissertations

This research focuses on the field of surface nanobioscience, wherein different nanosurfaces that will be used as working electrodes in the electrochemical cell are manufactured and surface modified to understand the critical binding interactions between biologically significant molecules like proteins, carbohydrates, small drug molecules, and glycoproteins. This research is essential if we are to determine whether a synthetic molecule can serve as a therapeutic candidate or diagnose a disease in its early stages. In order to fully understand the binding interactions, the study begins with defining some of the fundamental concepts, principles, and analytical tools for biosensing.

Afterwards, we addressed …

Molecular Mechanisms Of Amyloid-Like Fibril Formation, Sharareh Jalali

Dissertations

Proteins play a critical role in living systems by performing most of the functions inside cells. The latter is determined by the protein's three-dimensional structure when it is folded in its native state. However, under pathological conditions, proteins can misfold and aggregate, accounting for the formation of highly ordered insoluble assemblies known as amyloid fibrils. These assemblies are associated with diseases like Parkinson's and Alzheimer's. Strong evidence suggests that three mechanisms are critical for forming amyloid fibrils. These mechanisms are the nucleation of amyloid fibrils in solution (primary nucleation) as well as on the surface of existing fibrils (secondary nucleation) …

Exploring Topological Phonons In Different Length Scales: Microtubules And Acoustic Metamaterials, Ssu-Ying Chen

Dissertations

The topological concepts of electronic states have been extended to phononic systems, leading to the prediction of topological phonons in a variety of materials. These phonons play a crucial role in determining material properties such as thermal conductivity, thermoelectricity, superconductivity, and specific heat. The objective of this dissertation is to investigate the role of topological phonons at different length scales.

Firstly, the acoustic resonator properties of tubulin proteins, which form microtubules, will be explored The microtubule has been proposed as an analog of a topological phononic insulator due to its unique properties. One key characteristic of topological materials is the …

Continuum Modeling Of Active Nematics Via Data-Driven Equation Discovery, Connor Robertson

Dissertations

Data-driven modeling seeks to extract a parsimonious model for a physical system directly from measurement data. One of the most interpretable of these methods is Sparse Identification of Nonlinear Dynamics (SINDy), which selects a relatively sparse linear combination of model terms from a large set of (possibly nonlinear) candidates via optimization. This technique has shown promise for synthetic data generated by numerical simulations but the application of the techniques to real data is less developed. This dissertation applies SINDy to video data from a bio-inspired system of mictrotubule-motor protein assemblies, an example of nonequilibrium dynamics that has posed a significant …

Characterization And Genomic Analysis Of Two Escherichia Coli O157:H7 Bacteriophages Isolated From Pigeons, Mohamad I. Alolama

Dissertations

Enterohemorrhagic Escherichia coli, also known as EHEC, is a subset of Shiga toxin-producing E. coli (STEC), and it has recently been identified as one of the principal foodborne pathogens. E. coli O157:H7 is the most important serotype of STEC for its role in causing foodborne illnesses. E. coli O157:H7 could cause various gastroenteritis symptoms such as diarrhea, hemolytic uremic syndrome, hemorrhagic colitis, and thrombotic thrombocytopenic purpura and may cause death. Elimination of E. coli O157:H7 during food processing and storage is a possible solution. Bacteriophages have a significant impact on bacterial populations in nature due to their ability to …

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Role Of Micrornas In Intestinal Inflammation And Barrier Homeostasis After Alcohol And Burn Injury, Caroline J. Herrnreiter

Dissertations

MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA expression after alcohol and burn injury and elucidate their impact on inflammation and barrier integrity. In a more targeted approach, we began by focusing on anti-inflammatory miRNAs that, when downregulated, could exacerbate inflammation and result in intestinal barrier disruption. Using a mouse model of acute ethanol intoxication …

Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary

Dissertations

The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ into the endoplasmic reticulum of cells to establish a reservoir for Ca2+ signaling. In the heart, the activity of this transporter is tightly controlled via direct interactions with two competing regulatory micropeptides: phospholamban (PLB) and dwarf open reading frame (DWORF). PLB inhibits SERCA, while DWORF activates SERCA. These competing interactions determine cardiac performance by modulating the Ca2+ signals that drive the contraction/relaxation cycle. Previous studies indicated these SERCA-micropeptide interactions are Ca2+-sensitive; SERCA binds PLB more avidly at low cytoplasmic [Ca2+] but binds DWORF better when [Ca2+] is high. Here, FRET-microscopy demonstrated that this …

Interactions Of Amyloid Peptides With Lipid Membranes, Yanxing Yang

Dissertations

The aggregation of amyloid proteins into fibrils is a hallmark of several diseases including Alzheimer’s (AD), Parkinson’s, and Type II diabetes. This aggregation process involves the formation of small size oligomers preceding the formation of insoluble fibrils. Recent studies have shown that these oligomers are more likely to be responsible for cell toxicity than fibrils. A possible mechanism of toxicity involves the interaction of oligomers with the cell membrane compromising its integrity. In particular, oligomers may form pore-like structures in the cell membrane affecting its permeability or they may induce lipid loss via a detergent-like effect. This dissertation aims to …

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Investigating The Involvement Of The Tick Vector In The Induction Of Alpha-Galactose Hypersensitivity (Alpha-Gal Syndrome, Red Meat Allergy) In The United States., Gary Crispell

Dissertations

Alpha-gal syndrome (AGS or sometimes called red meat allergy) is a result of the development of specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) after a person has had exposure to tick bites. This dissertation investigates four common tick species found in North America: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) for the presence of α-gal by utilizing a combination of immunoproteomic approaches and carbohydrate analysis techniques.

Anti-α-gal IgM antibodies (M86) were used in immunoblotting to detect …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Structural And Transient Kinetic Analysis On Mechanism-Based Inactivators Of Human Ornithine Aminotransferase, Arseniy Butrin

Dissertations

HCC, Hepatocellular carcinoma, MBI, Mechanism-based inactivator, OAT, Ornithine Aminotransferase

The Roles Of A Probiotic Exopolysaccharide In Breast Cancer, Mai Rachel Nguyen

Dissertations

breast cancer, exopolysaccharide, probiotic

Immune Cell-Protein Interactions In Alzheimer’S Disease, Kapur Dhami

Dissertations

Misfolded protein aggregates are one of the significant contributing factors in many neurogenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others. My PhD research project was to study various aspects of amyloid-β peptide, a 40-42-residue peptide and the primary component of the senile plaques found in Alzheimer’s disease (AD) brains. One objective of my research was to purify and characterize the intermediate Aβ42 species using an array of biophysical techniques like size exclusion chromatography, fluorescence assays, circular dichroism, cellular assays, and protein assays. The other major research thrust of my project was to study the role of microglial …

Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett

Dissertations

2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …

Investigating The Role Of Fun30, A Chromatin Remodeler, In Dna Repair, Mehwish Iqbal

Dissertations

The repair of DNA double-strand breaks (DSBs) is crucial for maintaining genome stability. DSB repair needs to take place within the complex organization of the chromatin, and this requires changes in the chromatin structure adjacent to DSB sites. These changes occur through covalent histone modifications that alter histone-DNA contacts as well as by the action of ATP-dependent chromatin remodelers. Many chromatin remodelers, including Fun30, are involved in DSB repair. Fun30 facilitates DNA end resection at DSB site during the homologous recombination repair pathway. Apart from its role in DNA repair, Fun30 promotes gene silencing at heterochromatic loci such as telomeres, …

Delineating The Exocytic Fusion Machinery Required For Mast Cell Exocytosis, Pratikshya Adhikari

Dissertations

Mast cells undergo exocytosis to release a wide array of inflammatory mediators by utilizing membrane fusion proteins-SNAREs (soluble-N-ethyl-maleimide sensitive factor attachment protein receptor) along with essential regulatory Munc18 and Munc13 proteins. Accumulating evidence in mast cell biology suggests the existence of distinct pools of mast cell mediators. However, the precise mechanism underlying the release of each mast cell mediator is not clear. To determine whether different exocytic machineries are required for differential mediator release, I used reconstitution to investigate the differential role of Munc18s in fusion machinery regulation. Munc18a and Munc18c stimulated VAMP2 and VAMP3-mediated lipid mixing, whereas Munc18b only …

Abl2 Promotes Alcohol-Associated Liver Disease Via Ppar Gamma Regulation, Gregory Malnassy

Dissertations

Alcohol-associated liver disease (AALD) is an umbrella term for a spectrum of diseases resulting from chronic alcohol (e.g. ethanol) abuse ranging in severity from reversible conditions such as alcohol-induced steatosis to advanced and largely irreversible liver pathologies including alcoholic steatohepatitis (ASH), alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). AALD is one of the primary causes of chronic liver disease worldwide and accounts for 44% of liver disease deaths in the United States. Drinking rates, both in the United States and globally, have increased year over year for the past three decades, a trend which has resulted in significantly …

Granulins In Norm And Neurodegenerative Pathologies, Anukool Bhopatkar

Dissertations

Granulins (GRNs) are small, cysteine-rich modules produced from the proteolytic cleavage of the precursor protein called progranulin (PGRN). GRNs are present in the form of seven tandem repeats within the precursor and are known to be produced in the extracellular and in lysosomal environments. In physiology, PGRN and GRNs plays pleiotropic roles such as neuronal growth and differentiation, immunomodulation, wound healing. Recent studies have implicated pathological role for PGRN in Alzheimer disease (AD) and frontotemporal dementia (FTD) but specific mechanism(s) remains unclear. However, potential interactions between GRNs and Ab42 and TDP-43 seem like a plausible underlying mechanism. Studies presented here …

Dicer Represses Antiviral Innate Immunity Pathways In Mouse Embryonic Stem Cells, Chandan Gurung

Dissertations

Recent studies have demonstrated that embryonic stem cells (ESCs) are deficient in expressing type I interferons (IFN), the cytokines that play key roles in antiviral responses. However, the underlying molecular mechanisms and biological implications of this finding are poorly understood. In this study, I used a synthetic RNA-based assay that can simultaneously assess multiple forms of antiviral responses in ESCs. Dicer is an enzyme essential for RNA interference (RNAi), which is used as a major antiviral mechanism in invertebrates but not clear in vertebrates. RNAi activity is detected in wild-type ESCs but is abolished in Dicer knockout ESCs (D−/−ESCs) as …

Molecular Mechanism Of Action Of The Natural Polyphenolic Compound And The P300 Inhibitor “Carnosol” Against The Triple Negative Breast Cance, Halima Ali Mohammed Salem Alsamri

Dissertations

Carnosol, a naturally occurring Phyto polyphenol found in sage, oregano, and rosemary, has been extensively studied by our laboratory for its anticancer effects in various types of cancer. In human Triple-Negative Breast Cancer (TNBC), carnosol was shown to inhibit cellular viability, colony growth, induced cell cycle arrest, autophagy, and apoptosis. Nonetheless, very little is known about the molecular mechanism of action. In the current study, the ability of carnosol to inhibit metastasis and tumour growth was examined. Wound healing and invasion assays revealed that carnosol inhibited migration and invasion at non-cytotoxic concentrations of MDA-MB-231 cells. Also, carnosol was found to …

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is …

The Role Of The Msaabcr Operon In Cell Wall Integrity And Programmed Cell Death During Biofilm Development, Bibek G C

Dissertations

Staphylococcus aureus is an important human pathogen in both community and health care settings. Biggest challenges with S. aureus as a pathogen is its ability to acquire antibiotic resistance and produce robust biofilms. In this work, we investigated the nature of the cell wall defect in the msaABCR operon mutant in the Mu50 (VISA) and USA300 LAC methicillin-resistant Staphylococcus aureus (MRSA) strains. Results showed that msaABCR-mutant cells had decreased cell wall thickness and cell wall crosslinking in both strains. These defects are most likely due to increased murein hydrolase activity and/or nonspecific processing of murein hydrolases mediated by increased …

Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal

Dissertations

Glycoalkaloids (GAs) are secondary metabolites found mostly in higher plant species and some marine invertebrates. They are known to form complexes with 3β-hydroxy sterols such as cholesterol causing membrane disruption. So far the visual evidence showcasing the complexes formed between glycoalkaloids and sterols has been mainly restricted to some earlier studies using Brewster angle microscopy. This study aimed to develop a method for topographic and morphological analysis of sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of monolayers comprising of glycoalkaloid tomatine, sterols, and lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method used required minimal …

The Role Of Nutrient Sensitive Protein O-Glcnacylation In Developmental Cortical Neurogenesis, Shama Parween

Dissertations

The nutrient responsive O-GlcNAcylation is a dynamic, posttranslational protein modification present on many nucleocytoplasmic and mitochondrial proteins. Previous research has indicated that hyperglycaemia increases the levels of total O-GlcNAcylation within cells. Transcription factors and histones are among hundreds of proteins that have been reported to be O-GlcNAcylated and have importance in cell fate determination during cell growth, proliferation, and differentiation. However, the role of protein O-GlcNAcylation in epigenome control in response to nutritional perturbations is poorly understood. Hyperglycaemia induced protein O-GlcNAcylation have been linked to several pathologies, including obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases. …

Reconstituting The Cyanobacterial Circadian Clock In Vitro, Pyong Hwa Kim

Dissertations

Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the "ticking" of the oscillator can be reconstituted inside a test tube just …

Molecular Mechanism Of Cyanobacteria Circadian Clock Oscillator And Effect Of Co Factors On Its Oscillation, Manpreet Kaur

Dissertations

The circadian rhythms arise as an adaptation to the environmental 24-hour day and night cycle due to Earth's rotation. These rhythms prepare organisms to align their internal biological activities and day to day behavior or events with the environmental change of the 24-hour day and night cycle. Circadian rhythms are found widely in all living kingdoms of life on Earth. Cyanobacteria are photosynthetic prokaryotes which first used to study these circadian rhythms. Among cyanobacterial species, Synechococcus elongatus PCC 7942 (henceforth, S. Elongatus) is the simplest organism with a durable and sturdy circadian clock and is study as a model organism. …