Biochemistry, Biophysics, and Structural Biology Commons^™

Evolutionarily Conserved Functions Of The Gene Frazzled In Midline Axon Guidance In Drosophila Melanogaster And Tribolium Castaneum., Piyasi Ghosh

Graduate Theses and Dissertations

Axon guidance in bilaterians is often controlled by various signaling pathways in the nervous system, which determine the fate of the axons if they cross the midline or not. One such pathway involved is the ligand-receptor pair Netrin (Net) and Frazzled (Fra), which is also known as the attractive pathway that promotes midline crossing axons in insects and other bilaterians. Orthologs of the pathway ligand Netrins and their receptors Frazzled [Fra] in insects and Deleted in Colorectal cancer [DCC] in vertebrates are widely conserved in bilaterians. How well these regulatory roles of the protein are conserved is poorly understood. In …

Bacterial Chondronecrosis With Osteomyelitis In Broiler Chickens: Experimental Lameness And Additive Probiotic Treatments, Amanda Anthney

Graduate Theses and Dissertations

With the global population already surpassing 8.2 billion and expected to reach 9.7 billion by 2050, the poultry industry has seen a surge in demand due to its unmatched efficiency and affordability for consumers across the globe. Selective breeding and quality nutrition developments since the industry's commercialization have allowed producers to grow broilers up to 7 pounds by market age. While this extraordinarily efficient process has allowed quality poultry products to be available worldwide, the modern-day broiler has developed a multitude of musculoskeletal issues. Due to the lack of integral skeletal development to match the rapid production of muscle tissue, …

Intraspecific Genetic Variation In Green Salamanders (Aneides Aeneus) At Bays Mountain Park, Brianna Drake

Electronic Theses and Dissertations

Accurate taxonomy is crucial for conserving vulnerable cryptic species like the green salamander (Aneides aeneus) in the Southern Appalachian Mountains. Prior studies identified three distinct lineages within the A. aeneus complex: Northern Appalachians, Southern Appalachians, and Blue-Ridge Escarpment. One previously collected sample indicated green salamanders in northeast Tennessee fit within the Northern lineage. The present study uses molecular data of A. aeneus at Bays Mountain Park (BMP) in Kingsport, Tennessee, to determine where the BMP population fits within these lineages. It was hypothesized that individuals from BMP belong in the northern lineage. Tail tips were collected from thirty-four …

Transcription Factor Y- Box Binding Protein 1 (Ybx1) Enhances Sorafenib Resistance And Tumorigenic Capacities In Hepatocellular Carcinoma (Hcc), Dennis Kwabiah

Theses and Dissertations

Hepatocellular carcinoma (HCC) is the most common liver cancer, with early-stage cases potentially benefiting from surgical treatments like liver transplantation and hepatectomy. However, advanced HCC stages have poor prognosis due to resistance to therapies, especially sorafenib, a tyrosine kinase inhibitor approved for late-stage HCC. Despite its clinical use, sorafenib has limited efficacy in prolonging survival, and the mechanisms of resistance remain unclear. Analysis of The Cancer Genome Atlas (TCGA) HCC dataset shows elevated Y-box binding protein 1 (YBX1) expression in HCC tumors compared to normal liver tissues. Previous studies have indicated that YBX1 is involved in drug resistance in various …

Investigation Into Mycorrhizae Associated With Native Venus' Flytrap Root Tissue, Anna Carnaggio

Electronic Theses and Dissertations

Dionaea muscipula, a plant commonly known as the Venus' flytrap, is found native to the southeast corner of North Carolina and the northeast corner of South Carolina. Several populations of native Venus' flytraps are known to exist in the nutrient-poor peat bog conditions in and around Lewis Ocean Bay Heritage Preserve (LOBHP) in Northeastern South Carolina. Anthropogenic pressures in Horry County, specifically surrounding LOBHP, have resulted in a loss of habitat for several native and endangered species. As a result, conservation efforts are focused on relocating native Venus' flytraps into adjacent habitats to ensure survival. This is only a temporary …

Amyloid Aggregation And Mitigation, Zhenzhen Zhang

All Dissertations

The buildup of protein in tissues and organs plays a major role in unfunctional several serious diseases, including Alzheimer’s disease, Parkinson’s disease, and Type 2 diabetes, each tied to specific proteins that form harmful amyloid deposits. Amyloid aggregation typically follows a sigmoidal kinetic curve, beginning with a slow lag phase, followed by rapid fibril growth, and eventually reaching a plateau where mature, stable fibrils are formed. However, the early stage of aggregation remains particularly difficult to capture experimentally due to the highly dynamic nature and low abundance of small oligomeric species. In this dissertation, we employed discrete molecular dynamics (DMD) …

Structure Disorder And Magnetic Behavior Of An Olivine-Type Cathode Material, Hamida Hassan, Madalynn Marshall

Symposium of Student Scholars

Our research investigates the structure disorder and magnetic behavior of Li(Mn,Fe)PO₄, an olivine-type material relevant for lithium-ion battery applications. Using single-crystal neutron diffraction at Oak Ridge National Laboratory, we precisely determined Mn and Fe occupancy, revealing a 56% Fe and 44% Mn distribution at the atomic 4c site within the Pnma space group. Additionally, we observed significant lithium site vacancies (78% occupied), influencing the material's electrochemical and magnetic properties. The varying Mn/Fe ratio affected spin reorientation transitions, shifting from antiferromagnetic alignment along the a-axis to the b-axis. Our findings provide crucial insights for optimizing olivine-based cathodes, enhancing energy …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Cloning The Yersinia Enterocolitica Alkaline Phosphatase For An Affinity Chromatography Ligand, Flavio E. Arellano

ATU Scholars Symposium

Alkaline phosphatase (ALP) is an enzyme responsible for the dephosphorylation of extra-cytoplasmic molecules. Conversion to a neutral molecule enhances their ability to pass through cell membranes. When microbes such as Yersinia enterocolitica are ingested, they are exposed to large changes in pH level. These changes range from ~pH6.5 in the oral cavity to pH 2 in the stomach and pH 8 in the mid-intestine. The ability of microorganisms to survive this change in pH it largely dependent on their ability to change which proteins are expressed at differing pH levels or their ability to modify those proteins to meet the …

Glycosylation Of Serine/Threonine-Rich Intrinsically Disordered Regions Of Membrane-Associated Proteins In Streptococci., Mohammad M Rahman, Svetlana Zamakhaeva, Jeffrey S. Rush, Catherine T Chaton, Cameron W Kenner, Yin Mon Hla, Ho-Ching Tiffany Tsui, Vladimir N Uversky, Malcolm E Winkler, Konstantin V Korotkov, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Proteins harboring intrinsically disordered regions (IDRs) lacking stable secondary or tertiary structures are abundant across the three domains of life. These regions have not been systematically studied in prokaryotes. Here, our genome-wide analysis identifies extracytoplasmic serine/threonine-rich IDRs in several biologically important membrane-associated proteins in streptococci. We demonstrate that these IDRs are glycosylated with glucose by glycosyltransferases GtrB and PgtC2 in Streptococcus pyogenes and Streptococcus pneumoniae, and with N-acetylgalactosamine by a Pgf-dependent mechanism in Streptococcus mutans. The absence of glycosylation leads to a defect in biofilm formation under ethanol-stressed conditions in S. mutans. We link this phenotype to the C-terminal IDR …

The Chemistry Of Decomposition: The Mechanisms To Decay The Human Body, Lydia J. Buxa

Senior Honors Theses

Taphonomic analysis separates decomposition into four major stages: fresh, early decomposition, advanced decomposition, and skeletonization. It is easy to demarcate the observable changes to the body, but it is far more difficult to know what underlying biochemical processes are occurring. Fresh decomposition begins with algor mortis, livor mortis, and rigor mortis, which sets the stage for the major workforces of decomposition: autolysis and putrefaction. The external signs of decomposition appear in early decomposition, which can be attributed to the breakdown of proteins, lipids, carbohydrates, and nucleic acids. This also leads to major changes in the moisture levels during advanced decomposition, …

Metabolic And Microbial Crossroads: Sodium-Glucose Cotransporter-2 Inhibitors And Urinary Tract Infections In (Asian) Diabetes Care, Rob E. Carpenter

Human Resource Development Faculty Publications and Presentations

The global rise of type 2 diabetes, particularly in Asian populations, has led to widespread adoption of sodium-glucose cotransporter-2 (SGLT2) inhibitors for glycemic control. While effective, these agents elevate the risk of urinary tract infections (UTIs) by inducing glycosuria, which creates a nutrient-rich environment that favors uropathogen growth. Asian individuals may be disproportionately vulnerable to SGLT2 inhibitor–associated UTIs due to a confluence of factors, including lower body mass index, increased visceral adiposity, congenital urinary tract anomalies, and genetic polymorphisms that impair uroepithelial integrity and immunity. This review integrates emerging evidence on the molecular, anatomical, and immunometabolic mechanisms that underlie infection …

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …

Exploring The Role Of Azoreductase Enzymes In Drug Metabolism: Implications For Personalized Medicine, Najoude Claude, Robert Ghergurovich

Chemistry & Biochemistry Student Scholarship

Najoude Claude ’26, Biology major

Robert Ghergurovich ’26, Biochemistry major

Faculty mentor: Dr. Tyler Stack, Chemistry and Biochemistry

The gut microbiome hosts trillions of microorganisms that metabolize xenobiotics such as drugs and food dyes. Individual differences lead to variable drug metabolism. We studied two azoreductases: E. coli’s P41407 and Alistipes sp. CHKCL003’s A0A143XFE8. Enzyme P41407 acted on methyl red and ethyl red, while A0A143XFE8 acted on these and also on phenol blue, HMND, and sunset yellow. We propose these enzymes function as quinone reductases, requiring a quinone-like intermediate. Three synthesized compounds confirmed similar kinetics. In conclusion, these insights significantly advance …

Discovery, Purification And Annotation Of Four Novel Mycobacteriophages In New England, Mason Krawczynski

Chemistry & Biochemistry Student Scholarship

Mason Krawczynski ’26, Biology and Psychology major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophages are viruses that infect bacteria of the Mycobacterium genus. Several thousand mycobacteriophages have been discovered, isolated, and characterized to advance the current understanding of their genomic diversity. The mycobacterium phage selection proves valuable, as they have a broad host range and potential for therapeutic application to treat pathogenic and antibiotic-resistant mycobacteria, such as Mycobacterium tuberculosis, the causative agent of tuberculosis infection. Kraw was isolated from a soil sample collected in Oaks Bluff, Massachusetts, on the island of Martha’s Vineyard in July 2023. FairyPath, Calvinny, …

Tools For Harnessing Atropisomerism In 1-Aryl-Β-Carbolines, Cristina Díaz, Malaquias Loiza, Josef Crenshaw, Brian Ladino, Elizabeth Perda, Alma Martinez, Joseph Mazzucca, John Stathoulopoulos

Chemistry & Biochemistry Student Scholarship

Cristina Díaz ’25, Chemistry major

Malaquias Loiza ’26, Biochemistry major

Josef Crenshaw ’28, Biochemistry major

Brian Ladino ’28, Biochemistry major

Elizabeth Perda ’26, Biochemistry major

Alma Martinez ’26, Biochemistry major

Joseph Mazzucca ’25, Biochemistry major

John Stathoulopoulos ’26, Chemistry major

Faculty mentor: Dr. Seann Mulcahy, Chemistry and Biochemistry

Axially chiral molecules with high barriers to rotation are becoming increasingly more prominent in drug discovery, chemical biology, and materials science. We have shown that 1-aryl-β-carbolines exhibit high configurationally stability, with barriers to rotation greater than 30 kcal/mol and have recently disclosed an asymmetric synthesis of these molecules. In this presentation, we …

Discovery, Purification And Annotation Of A Novel Mycobacteriophage Discovered On The Providence College Campus, Jenna Greene

Chemistry & Biochemistry Student Scholarship

Jenna Greene ’26, Biochemistry major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Bacteriophages—viruses that infect bacteria—offer a promising alternative to antibiotics in the face of rising antibiotic resistance. In this project, I isolated a novel phage from a soil sample collected in front of Raymond Dining Hall at Providence College. Using Mycobacterium smegmatis as the host, the sample underwent multiple rounds of purification until a single phage, named GMonster (a nod to my family nickname, “Greene Monster”), was isolated. GMonster was submitted to the PhagesDB database and confirmed through sequencing to belong to the A1 cluster—the first of its …

Exploring An Electron-Rich Iron Tricarbonyl Complex Containing An Α-Diimine Ligand, Joseph Maher

Chemistry & Biochemistry Student Scholarship

Joseph Maher ’25, Chemistry major

Faculty mentor: Dr. Maria Carroll, Chemistry and Biochemistry

The combustion of fossil fuels increases atmospheric CO2, making hydrogen a promising cleaner energy alternative. Pt has been able to facilitate this reaction efficiently, however, it is expensive and scarce. Fe has shown promise in facilitating 2-electron transfers when bound to redox-active ligands. Reacting the redox-active CyDABMe with benzylidene acetone iron tricarbonyl (bdaFe(CO)3) forms Fe[CyDABMe](CO)3, with vCO values ~10 cm-1 lower than FeArDABMe(CO)3, indicating increased electron density. The reduction potential of CyDABMe was probed using Zn[CyDABMe]Cl2, showing a reduction at 200 mV more negative than Zn[ArDABMe]Cl2. X-ray …

Effects Of Hyperglycemia In Cognition And Sex, Erin E. Mcdonald

Senior Honors Theses

An empirical study tested the effects of Type 1 Diabetes (T1D) on cognitive function in a hyperglycemic mouse model. Strong correlations between mental illnesses, such as major depressive disorder, neuropathologies like Alzheimer’s disease, and diabetes suggest comorbid pathology. Considering the prevalence of both T1D and cognitive decline within the general population, the findings were relevant and aimed to identify early signs of cognitive decline in diabetic patients. Behavioral tests and immunohistochemical staining were utilized to determine the cognitive function of the mice, revealing decline or deterioration caused by hyperglycemia. Data gathered from the hyperglycemic or control mice were analyzed based …

Developing An Unfolding-Incorporated Coarse-Grained Polymer Model For Fibrinogen To Study The Mechanical Behaviour, Vivek Sharma, Poulomi Sadhukhan

Northeast Journal of Complex Systems (NEJCS)

Fibrinogen is a protein found in blood that forms Fibrin polymer network to build a clot during wound healing process when there is a cut in the blood vessel. The fibrin fiber is highly stretchable and shows a complex mechanical properties. The fibrin monomer, Fibrinogen, has a very complex structure which is responsible for its unusual elastic behaviour. In this work, we focus on mechanism of unfolding of D-domain of Fibrinogen, and study its effect in the mechanical behaviour. We develop a coarse-grained (CG) bead-spring model for Fibrinogen which captures the unfolding of folded D-domains along with other necessary structural …

Trenching And Compost Sustain Grain Yield Increases Over Nine Years On Deep Sands But At A Cost, David J.M. Hall, Tom J. Edwards

Grain and Other Field Crops Research Articles

Context. Crops grown on deep sands on the south coast of WA are limited by soil physical and chemical properties including compaction and poor nutrition. Aims. Crops grown on deep sands on the south coast of Western Australia are limited by soil physical and chemical properties including compaction and poor nutrition. Our aim was to determine what effects deep-placed organic amendments have on soil properties and crop production in a deep sand and whether such amendments are profitable. Methods. A long-term field trial was conducted over nine years (2015–2023) to investigate soil amendments including lime (0 and …

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas

LSU Doctoral Dissertations

Protein-protein interactions vary among cell types and the localization of these interactions help to define protein function. The function of cystic fibrosis transmembrane conductance regulator (CFTR) is well established in the context of epithelial tissue due to the debilitating effects of its mutations that cause the disease cystic fibrosis. While in neurons a role has been established in our lab for CFTR in the regulation of cytosolic Cl- in retinal amacrine cells (ACs). This research sets out to learn if CFTR has a synaptic role. Exploring this potential role, localization of CFTR was examined using fluorescent and immunogold labeled transmission …

Antioxidant Properties Of Phytochemicals In Watercress And Mint Extracts In Serum Albumin, Perla Tovar

Undergraduate Research Conference

Hypothesis: Phytochemicals present in mint and watercress help stabilize protein under oxidative stress. Main Objective: Analyze the interaction of HSA with different phytochemicals present in mint extract.

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Missense Mutation Of Msh6 Leucine 696 Has No Apparent Effect On The Dna Mismatch Repair Process, Razan H. Hammad, Rafia Rashid, Essence Tarrence, Christopher Bolden, Joanna E. Haye-Bertolozzi

XULAneXUS

Lynch Syndrome and Constitutional Mismatch Repair Deficiency are human diseases implicated in mutations of DNA mismatch repair (MMR) genes. This experiment tested a mutation of an MMR gene, MSH6, and evaluated how the mutation affected overall MMR effectiveness. Using the yeast Saccharomyces cerevisiae, we performed the CAN1 forward mutation assay to study msh6-L696F and its implications in the MMR process. We hypothesized that there would be a significant change in molecular function in the Msh6 protein in the presence of this mutation. Bioinformatic tools predicted that this amino acid change would have deleterious effects on MMR function. However, …

Hexasodium Fytate (Snf472 Or Csl525) Inhibits Ectopic Calcification In Various Pseudoxanthoma Elasticum And Calcinosis Cutis Animal Models, Miguel Ferrer, Maria Pérez-Ferrer, Marc Blasco, Ida Jacobs, Qiaoli Li, Olivier Vanakker, Lisa Dangreau, Andrea López, Gianluca Malagraba, Firas Bassissi, Joan Perelló, Carolina Salcedo

Department of Biochemistry and Molecular Biology Faculty Papers

Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6^-/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6 …

The Fractography Of Bone: Impact Of Flat Bone And The Story It Tells, Abigail Hoffmeister, Chase Freeman, Brandon Mendoza, Nathaniel Fitch, Annie Markarian, Jack Tran, Joshua Lau, Nicholas Tran

Seaver College Research And Scholarly Achievement Symposium

Fractography as a method for fracture analysis has been applied widely to materials that range from glass to ceramics and polymers of varying compositions. Very limited research has been done, however, to apply this knowledge of fractography and fracture patterns to bone. With the goal of telling the story of how a bone was broken, this research focuses on observing known patterns of fracture in polymers, and applying these patterns to bone. For the purposes of this research, porcine scapulae were acquired, dissected from surrounding tissue, and broken using a standardized weight drop at varying heights. The fractured bone was …

Diets And Environmental Impacts - Generational Outlook, Aspen Hopper, Melanie Jex

Student Research Symposium

How different diets impact the environment: Are we aware?

Determining The Kinetic Basis Of Crispr-Cas12a2 Function, Sobita Kunwar, Thomson Hallmark, Dylan Keiser, Bronson Naegle, Sudeshna Manna, Aaron Thomas, Chase L. Beisel

Student Research Symposium

CRISPR- Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated) systems are bacterial adaptive immune systems that protect bacteria against mobile genetic elements such as viruses and plasmids^1,2.

Solving The Structure Of An Ancestral Protein Tyrosine Phosphatase, Natalie Turcsanski, Edna Armah

Student Research Symposium

Protein tyrosine phosphatases (PTPs) regulate cell signaling by removing phosphate groups from tyrosine residues. Malfunction of these enzymes can lead to diseases such as diabetes and cancer. A conserved feature among PTPs is the catalytic acid loop, essential for phosphate removal. Computational analysis of PTP structures revealed that ancestral PTPs have considerable variation in conformations of this loop, sparking interest in their further study. The Asgard group, identified as ancestral to eukaryotic PTPs, was successfully expressed and purified under optimized conditions. Current efforts focus on optimizing crystallization to obtain larger crystals for structural analysis. This project will investigate the allosteric …