Biochemistry, Biophysics, and Structural Biology Commons^™

Probing The Secondary Structure Of Intrinsically Disordered Squid Reflectin Protein Through Ssnmr, Harriet Austin

Digital Repository: Showcase of Undergraduate Research Excellence

No abstract provided.

Optimization Of Dapoxyl Aptamer For Label-Free Bioanalysis, Jack E. Mordeson, Ryan P. Connelly, Pedro F. Madalozzo, Yulia Gerasimova

Digital Repository: Showcase of Undergraduate Research Excellence

No abstract provided.

Fluvial Sediment Organic Matter Degradation Identified With Elemental And Isotopic Fate During Laboratory Incubation, Brenden Riddle

Theses and Dissertations--Civil Engineering

Fluvial sediment is well recognized as a critical factor in both carbon and nutrient budgets within stream systems. However, we find very few studies of reactivity and isotope enrichment for stream water from agricultural and urban streams and the class of substrate known as fluvial sediment organic matter. This study investigated the hypothesis that fluvial sediment is subject to degradation even though many previous studies have considered this class of substrate generally inert. Therefore we qualify that elemental and isotopic signatures of fluvial sediment organic matter should be considered potentially non-conservative when used in tracer studies. Methods applied to this …

Physicochemical Characterization, Structural Determination, And Molecular Dynamic Modeling Of Proso Millet Proteins For Enhanced Food Functionality, Felix Akharume

Theses and Dissertations--Biosystems and Agricultural Engineering

More than one-third of Americans today incorporate plant-based protein into their diet and about 40% believed that plant-based protein is healthier than animal protein, especially Millennials. The increasing global demand for plant-based proteins driven by the high cost of animal proteins, consumers’ desire for lean protein, vegetarianism, and the need for more sustainable green protein products have necessitated research into alternate emerging and underutilized sources of protein to complement or supplement the major plant protein in the market- soy, pea, and gluten. Therefore, this dissertation is focused on the valorization of the proteins in proso millet. Specifically, this work focused …

Epigenetic Regulation Of Hormone Action In The Red Flour Beetle, Tribolium Castaneum (Herbst), Smitha George

Theses and Dissertations--Entomology

Hormones are the chemical communication signaling molecules released into the body fluid to stimulate target cells of multicellular organisms. Two major hormones, ecdysteroids (20-hydroxyecdysone, 20E) and juvenile hormones (JH), regulate a wide variety of physiological and developmental processes in insects. Therefore, hormones have been extensively studied and are attractive targets for the development of target-specific insect control methods. Recent studies suggest that epigenetics adds another layer of regulation to explain multiple functions of the same circulating hormone in different tissues and at various time points. In my dissertation, I focused on a major post-translational modification, ‘acetylation,’ to elucidate the epigenetic …

Impact Of Cold Plasma Processing On Major Peanut Allergens, Harshitha Venkataratnam, Orla Cahill, Chaitanya Sarangapani, Patrick J. Cullen, Catherine Barry-Ryan

Articles

Cold plasma is emerging as a novel food processing technology, with demonstrated efficacies for microbial inactivation and residual chemical dissipation of food products. Given the technology’s multimodal action it has the potential to reduce allergens in foods, however data on the efficacy and mechanisms of action are sparse. This study investigates the efficacy of cold plasma on major peanut allergens (Ara h 1 and Ara h 2). For this purpose, dry, whole peanut (WP) and defatted peanut flour (DPF) were subjected to an atmospheric air discharge using a pin to plate cold plasma reactor for different treatment durations. With increases …

Pt(Iv) Pro-Drugs With An Axial Hdac Inhibitor Demonstrate Multimodal Mechanisms Involving Dna Damage And A Poptosis Independent Of Cisplatin Resistance In A2780/A2780cis Cells, Awatif Rashed Z. Almotairy, Diego Montagner, Liam Morrison, Michael Devereux, Orla Howe, Andrea Erxlebena

Articles

Epigenetic agents such as histone deacetylase (HDAC) inhibitors are widely investigated for use in combined anticancer therapy and the co-administration of Pt drugs with HDAC inhibitors has shown promise for the treatment of resistant cancers. Coordination of an HDAC inhibitor to an axial position of a Pt(IV) derivative of cisplatin allows the combination of the epigenetic drug and the Pt chemotherapeutic into a single molecule. In this work we carry out mechanistic studies on the known Pt(IV) complex cis,cis,trans-[Pt(NH3)2Cl2(PBA)2] (B) with the HDAC inhibitor 4-phenylbutyrate (PBA) and its derivatives cis,cis,trans-[Pt(NH3)2Cl2(PBA)(OH)] (A), cis,cis,trans-[Pt(NH3)2Cl2(PBA)(Bz)] (C), and cis,cis,trans-[Pt(NH3)2Cl2(PBA)(Suc)] (D) (Bz = benzoate, Suc …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Characterization Of An Aryl Piperazine/2-Hydroxypropyl-Β-Cyclodextrin Association, A Complex With Antidiabetic Potential, R. Devine, D.S.D. Martin, Gemma Kinsella, J.B.C. Findlay, J.C. Stephens

Articles

This study explores the molecular association between 4-(thiophen-2-yl)-1-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)butan-1-one (RTC1), an antidiabetic compound recently reported by our research group with challenging aqueous solubility, and 2-hydroxypropyl-β-cyclodextrin (HPBCD). The formation of a RTC1/HPBCD complex resulted in improved solubility. A phase-solubility diagram was used to determine the complex stability constant and stoichiometric ratio. 2D ¹H NMR spectroscopy was utilized to study the molecular interaction between RTC1 and HPBCD in the complex. Differential scanning calorimetry and scanning electron microscopy was also employed to confirm complex formation. In vitro biological evaluation, using a glucose uptake assay, showed that the homogeneous RTC1/HPBCD complex solution showed the …

Gravity-Drawing Flexible Silicone Filaments As Fiber Optics And Model Foldamers, Katherine Snell

CMC Senior Theses

Here, we present a method of gravity-drawing polydimethylsiloxane (PDMS) silicone fibers with application as fiber optics and as model foldamers. Beginning as a viscous liquid, PDMS is cured using heat until its measured viscosity reaches 4000 mPa•s. The semi-cured elastomer is then extruded through a tube furnace to produce thin (diameters on the order of hundred micrometers) filaments with scalable lengths. PDMS is biocompatible, gas-permeable, flexible, and hydrophobic. Additionally, the PDMS surface hydrophobicity can be modified via UV exposure, O2 plasma, and corona discharge. We demonstrate the patternibility (i.e patterns of hydrophobicity) of PDMS fibers, adding complexity to potential foldamer …

Characterization And Enzyme Engineering Of Laccases Towards Lignin Valorization In Aqueous Ionic Liquids, Joseph Stevens

Theses and Dissertations--Biosystems and Agricultural Engineering

Lignin is one of the most abundant polymers found in nature, making up 15 – 40% of the weight of terrestrial biomass. Due to the structural and monomeric heterogeneity of lignin, it is recalcitrant thermochemical and biological valorization methods. Converting lignin to value-added products via sustainable and cost-effective pathways will reduce waste and add value to future cellulosic biorefineries. Biological methods for lignin valorization (e.g. lignin degrading enzymes or microbes) is limited by low lignin solubility in biocompatible solvents, resulting in low product yield. Recent reports on biocatalysts for lignin valorization have focused on the lignolytic multicopper oxidase laccase, …

Investigation Of The Phenotypic Effect Of Mutating A Highly-Conserved Cysteine Residue In The Rna Polymerase Beta Prime Subunit Of E. Coli Rna Polymerase, Meg Dillingham

Mahurin Honors College Capstone Experience/Thesis Projects

All bacteria contain a multi-subunit RNA polymerase (RNAPs) that is essential for gene expression. Because of the centrality of these enzymes in cellular life, the structure and function of the various subunits is intensely studied. The primary sequence of the RNAP β’ subunit contains five cysteine residues that are highly conserved. Four of the cysteines coordinate a zinc atom and form the beta prime subunit zinc binding domain (ZBD). Mutation of any one of the ZBD cysteines is lethal to the cell. However, the role of the fifth residue (C58), which is located upstream of the ZBD cysteines, has not …

Investigating The Role Of Centromeric Repeats In Female Meiotic Drive, Jocelyn Crawford

CMC Senior Theses

Female meiotic drive is an unequal transmission of alleles that arises through the competition of paired chromosomes for inclusion in the egg, resulting in an increase in frequency of the driven alleles regardless of their effect on fitness of the individual. In Mimulus guttatus (monkeyflower) second filial generations, driven alleles display transmission advantages resulting in the virtual elimination of recessive homozygotes, while the equivalent lines lacking drive elements conform to traditional Mendelian segregation population ratios. Centromeres have been identified as mechanistic drive elements due to their role in chromosomal segregation during female meiosis, with Mimulus providing the best documented case …

Therapeutic Efficacy Of Umbilical Cordderived Stem Cells For Diabetes Mellitus: A Meta-Analysis Study, Dina H. Kassem, Mohamed M. Kamal

Pharmacy

Background: Stem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJMSCs) and umbilical cord blood (UCB) for DM. Methods: The clinical …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

The Effects Of Induced Polycystic Ovary Syndrome In Nag-1 Transgenic Mice, Nicholas Werner

All Master's Theses

Polycystic ovary syndrome (PCOS) is the leading cause of infertility among women in the US and the most common endocrine disorder among women. PCOS is characterized by cystic ovaries, hyperandrogenism (heightened levels of male sex hormones), altered menstrual cycles and various metabolic dysfunctions. The metabolic symptoms associated with PCOS are difficult to treat, as they are a result of hormonal imbalances, rather than diet. The human Non-Steroidal Anti-Inflammatory Drug Activated Gene (NAG-1) been shown to prevent diet-induced metabolic disorders and weight gain in mice. We hypothesized that the expression of NAG-1 may also prevent hormonal-induced metabolic disorders. To test this …

Acoustic Analysis Of Nomascus Gibbon Songs As A Potential Measure Of Current Health Status, Caroline Rowley

All Master's Theses

Post-release monitoring is vital to the rehabilitation process. Gibbons offer a unique challenge, as they are notoriously difficult to follow through the forest, but their duets offer a non-invasive window into their lives. The aim of this project is to create a method that will evaluate the health of rehabilitated and released gibbons through acoustic analyses. Gibbon duets are in part genetically determined, but learning may play a role in song development. Additionally, songs may indicate resource holding potential, and are vital to acquiring mates and producing offspring. Captive-raised gibbons are often denied the experience of co-singing with their parents, …

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance …

Application Of Β-Chloroenals: One-Pot Syntheses To Create Highly Variable, Functional, And Biologically Interesting Molecules, Julia Powell Siewert

Honors Theses

Pyrroles and pyrazoles are privileged structures which provide a molecular framework found in many different classes of bioactive compounds, thus rendering their syntheses useful in pharmaceutical drug development. Additionally, being able to selectively create these molecules with interesting substituents allows for different pharmacological and biological activities, such as antitumor and antibiotic effects. Our group has used β-chloroenals in the application of many different unique synthetic strategies in the past, and here I show that chloroenals can be used to synthesize novel 1,2,5 trisubstituted pyrroles as well as 1,5 di- and 1,4,5 trisubstituted pyrazoles in fewer steps and with milder conditions …

The Effects Of Signaling Molecules To Agrobacterium Tumefaciens Tumorigenesis At Plant Wound Sites, Nicole Walker

Honors Theses

Agrobacterium tumefaciens can live independently within soil before infecting its host (McCullen and Binns, 2006). The bacterium infects the plant through the rhizosphere, an area of soil along the plant root surface which contains microorganisms, making up the “external metabolome” (Bais et al. 2006). As these bacteria live in the rhizosphere, they are exposed to a multitude of chemical signals. These chemical signals include several conditions that must be met before the virulence machinery is expressed. These conditions include signaling from phenols and sugars as well as low PO4 levels and low pH. Upon wounding, sugars and phenols are released …

Therapeutic Dna: Delivery And As A Delivery Vehicle, Natalie J. Holl

Masters Theses

"A review of gene delivery methods and gene editing methods, as well as original research utilizing DNA as a delivery vehicle is presented in the following thesis. Thousands of diseases have been linked to genes. Gene therapy, either delivering therapeutic genes or editing DNA bases, has arisen as a treatment option with the potential to cure diseases, rather than just ease symptoms. Genes and editing tools need to be delivered to cells for these therapies to be effective and many techniques have been developed to address the issue of delivery. Nonviral and viral methods have been used to deliver nucleic …

Genomic-Based Identification Of Environmental And Clinical Listeria Monocytogenes Strains Associated With An Abortion Outbreak In Beef Heifers, Katherine J. Whitman, James L. Bono, Michael L. Clawson, John D. Loy, Joseph M. Bosilevac, Terrance M. Arthur, Jeff D. Ondrak

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages of L. monocytogenes (I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis of L. monocytogenes as a causative agent in disease outbreaks relies upon case …

Virus Purification Framework And Enhancement In Aqueous Two-Phase System, Pratik Umesh Joshi

Dissertations, Master's Theses and Master's Reports

Viral infections regularly pose detrimental health risks to humans. Preventing viral infections through global immunization requires the production of large doses of vaccines. The increasing demand for vaccines, especially during pandemics such as COVID-19, has challenged current manufacturing strategy to develop advanced unit operations with high throughput capability. Over the decade, the upstream processing responsible for synthesizing viral products in cell cultures has shown significant success in yielding high titers of viruses and virus-like particles. The progress in the upstream stage has now shifted the bottleneck to the downstream processing (DSP). Overlooked for decades, the DSP responsible for viral product …

Archaeosine Modification Of Archaeal Trna - A Role In Structural Stabilization, Ben Turner, Brett W. Burkhart, Katrin Weidenbach, Robert Ross, Patrick A. Limbach, Ruth A. Schmitz, Valérie De Crécy-Lagard, Kenneth M. Stedman, Thomas J. Santangelo, Dirk Iwata-Reuyl

Biology Faculty Publications and Presentations

Archaeosine (G+) is a structurally complex modified nucleoside found quasi-universally in the tRNA of Archaea and located at position 15 in the dihydrouridine loop, a site not modified in any tRNA outside of the Archaea. G+ is characterized by an unusual 7-deazaguanosine core structure with a formamidine group at the 7-position. The location of G+ at position 15, coupled with its novel molecular structure, led to a hypothesis that G+ stabilizes tRNA tertiary structure through several distinct mechanisms. To test whether G+ contributes to tRNA stability and define the biological role of G+, we investigated the consequences of introducing targeted …

An Assessment Of Convergence In The Feeding Morphology Of Xiphactinus Audax And Megalops Atlanticus Using Landmark-Based Geometric Morphometrics, Edward Chase Shelburne

Master's Theses or Doctor of Nursing Practice

Convergence is an evolutionary phenomenon wherein distantly related organisms independently develop features or functional adaptations to overcome similar environmental constraints. Historically, convergence among organisms has been speculated or asserted with little rigorous or quantitative investigation. More recent advancements in systematics has allowed for the detection and study of convergence in a phylogenetic context, but this does little to elucidate convergent anatomical features in extinct taxa with poorly understood evolutionary histories. The purpose of this study is to investigate one potentially convergent system—the feeding structure of Xiphactinus audax (Teleostei: Ichthyodectiformes) and Megalops atlanticus (Teleostei: Elopiformes)—using a comparative anatomical approach to assess …

Targeting The Nt17 Of The Huntingtin Protein Via Natural And Chemical Modifications: Impact On Aggregation And Membrane Interactions, Faezeh Sedighi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Huntington Disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine domain (polyQ) in the first exon of the huntingtin protein (htt-exon1). The major hallmark of HD is the accumulation of aggregates into proteinaceous inclusion bodies. PolyQ expansion in huntingtin promotes self-assembly into a variety of toxic aggregates such as oligomers, fibrils, and amorphous aggregates. The resulting heterogeneous mixture of distinct species makes it difficult to assign a toxic function to specific aggregate structures. In addition, htt interacts with a variety of membranous surfaces. The first 17 amino acids (Nt17) of htt directly flanking the polyQ domain functions …

Paper-Based Point-Of-Care Tools For Blood Testing, Xuefei Gao

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early detection of malignant disease is crucial for timely diagnosis and effective medical intervention, which significantly increases survival rates and reduce financial burden on patients. Biomarkers are becoming increasingly important in detection of malignant diseases, because they can be employed for indicating diseases, predicting risks and monitoring the progression of diseases. In addition, biomarkers show up at early stages of diseases in human tissues and fluids (e.g., blood, urine and saliva), which shows great promise for early disease detection. In this dissertation, paper-based lateral flow strips (PLFSs) have been developed for the detection of disease biomarkers, including protein biomarkers and …

Antibiotic Drug Nanocarriers For Probing Of Multidrug Abc Membrane Transporter Of Bacillus Subtilis, Pavan Kumar Cherukuri, Preeyaporn Songkiatisak, Feng Ding, Jeam-Michel Jault, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters can extrude a wide range of substrates, which cause multidrug resistance and ineffective treatment of diseases. In this study, we used three different sized antibiotic drug nanocarriers to study their size-dependent inhibitory effects against Bacillus subtilis. We functionalized 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm silver nanoparticles (Ag NPs) with a monolayer of 11-amino-1-undecanethiol and covalently linked them with antibiotics (ofloxacin, Oflx). The labeling ratios of antibiotics with NPs are 8.6 × 10², 9.4 × 10³, and 6.5 × 10⁵ Oflx molecules per NP, respectively. We designed …

Isothermal Environmental Heat Energy Utilization By Transmembrane Electrostatically Localized Protons At The Liquid-Membrane Interface, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

This study employing the latest theory on transmembrane electrostatic proton localization has now, for the first time, consistently elucidated a decades-longstanding bioenergetic conundrum in alkalophilic bacteria and more importantly discovered an entirely new feature: isothermal environmental heat utilization by electrostatically localized protons at the liquid-membrane interface. It was surprisingly revealed that the protonic motive force (equivalent to Gibbs free energy) from the isothermal environmental heat energy utilization through the electrostatically localized protons is not constrained by the overall energetics of the redox-driven proton pump system because of the following: (a) the transmembrane electrostatically localized protons are not free to move …

Complex Ciliary Flows Around Stentor Polymorphus In Solutions Of 2% Buttermilk And Chlamydomonas Reinhardtii, Eliana B. Smithstein

Scripps Senior Theses

Stentor are large, unicellular ciliates of the Heterotricha order. They live in both freshwater and marine habitats and are mostly found in ponds. I studied Stentor polymorphus, which is a species of Stentor only recently discovered to be lab culturable. They range from 0.5-1.5mm in length and are unusual because they live with endosymbiotic algae and are much more likely than other, more widely studied, species of Stentor to form aggregates while they are eating. There are three main components to this thesis: First, I established protocols for keeping a viable S. polymorphus culture, since no protocols had been …