Biochemistry Commons^™

Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet

Honors Scholar Theses

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and …

The Role Of Myosin L In The Survival Of Toxoplasma Gondii And The Importance Of Mlc1 For In Vitro And In Vivo Myosin F Motility, Victoria K. Yi

Honors Scholar Theses

My thesis discusses the work that I have conducted on two myosins in Toxoplasma gondii, which is an obligate intracellular parasite that has chronically infected around 10% of the American population. It causes toxoplasmosis and severe health consequences for individuals with compromised immune systems or when infections occur in utero. However, immunocompetent individuals are asymptomatic or present with subclinical symptoms. In the Heaslip lab, I investigated two myosins in the parasite: Myosin L and Myosin F. MyoL is an uncharacterized motor that localizes at the apical end of the parasite. It was shown to be important for parasite …

Characterization Of 3d Printed Microdialysis Probes For Solute Recovery And Non-Specific Adsorption, Bailey N. Scoggins

Chemistry & Biochemistry Undergraduate Honors Theses

Microdialysis is an important sampling technique that has uses in a wide range of disciplines, such as neuroscience and pharmacokinetics. 3D printing aims to address adaptability and customization issues that are present in standard “off-the-shelf” microdialysis probes. This work aims to lay the groundwork for characterizing a 3D printed microdialysis probe designed at the University of Arkansas. One experiment involved measuring solute recovery of caffeine as a function of flow rate of a standard CMA 11 probe to assess its membrane performance. The other goal was to learn about non-specific adsorption tendencies of enzymes (i.e., to what degree proteins stick …

The Expression Of Intestinal Tight Junction Proteins Induced By 1,25-Dihydroxyvitamin D3-Glycosides Supplementation To Reduce Bacterial Chondronecrosis With Osteomyelitis Lameness In Broilers, Kennedy M. Hicks

Biological Sciences Undergraduate Honors Theses

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a leading cause of lameness in broiler chickens, impacting animal welfare and commercial poultry production. Supplementation using organic trace minerals, vitamin D, probiotics, and prebiotics has been studied to mitigate BCO lameness incidences in broiler chickens. Our previous study demonstrated that feeding Panbonis®-G-1,25(OH)₂D₃ from Solanum glaucophyllum, containing 1 µg/kg G-1,25(OH)₂D₃, to broilers for the first 28 days of their production cycle reduced BCO lameness by approximately 50%. In this study, we investigated the impact of 1,25-dihydroxy vitamin D₃ supplementation on the expression of tight junction …

Bpa Adsorption On Microplastics In Different Chemical Conditions, Addison Zehren

University Honors Program Senior Projects

Microplastics (plastic particles < 5 mm in size) are increasingly seen as a health and environmental issue, both for their direct effects when ingested by living organisms and for their ability to adsorb and concentrate other pollutants. Current water treatment processes do not adequately remove microplastics from municipal water supplies, so a thorough understanding of how microplastics affect water quality is needed. The objective of this study is to evaluate the effects of certain water quality parameters on the ability of polystyrene microplastics (PS MPs) to adsorb Bisphenol A (BPA). BPA is an endocrine disruptor (chemically like estrogen) used in plastics which can be released into the environment and act as a water pollutant. Water quality chemical parameters investigated were chloride, nitrate, phosphate, and copper ions. Concentrations of each solute were selected based upon Environmental Protection Agency (EPA) guidelines and previous results obtained from testing Chicago River water samples. A constant amount of PS MPs and BPA were added to each sample and the mixtures were shaken for 5 days to allow time for the BPA to adsorb. The samples were then filtered and the amount of BPA left in the water was determined by measuring its UV absorbance on a UV-vis spectrophotometer. BPA concentrations decreased in the water indicating that it had been adsorbed onto the microplastic surface, with the highest adsorption present with copper, which reduced BPA concentrations from 6.7 mg/L to 3.9 mg/L. Statistical analyses showed differences between copper, phosphate, nitrate, and chloride (df = 9, p = 0.002). Future work can apply these results to investigate the implications of pollutant transportation in urban waterways like the Chicago River.

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Development And Functional Characterization Of Carbon Nanodot-Peptide Conjugates For The Treatment Of Bone Disease, Abigail Ali

Honors Theses

Carbon nanodots (CDs) synthesized from carbon nanopowder under acid oxidative conditions have unique bone-bind properties that could be exploited for theranostic purposes. In the zebrafish vertebrate model system, CDs bind to bone with high affinity and specificity, they don’t appear to bind to other tissues and they do not affect the bone physiology or animal viability. Thus, carbon-derived CDs could be developed for the delivery of pharmacological agents to bones to treat diseases such as osteoporosis. Biologicals such as peptides, proteins and antibodies are a new and exciting class of pharmacological agents that have been successfully used in treating complex …

Effect Of Glycation On The Binding Interactions Of Serum Albumin And Silver Nanoparticles, Megan Kirk

Celebrating Scholarship and Creativity Day (2018-)

Nanoparticles are particles ranging from 1-100 nanometers in size. Most nanoparticles, upon contact with biological matrices, are immediately coated with proteins, forming the protein corona, which can alter the structure and function of proteins. Despite the tremendous advancement of nanotechnology over the last decade, the interactions of nanoparticles with proteins are not well characterized. This project investigates the effect of glycation on the binding interactions of HSA, the most abundant protein in human blood, with silver nanoparticles using various spectroscopic techniques. This is important because in diabetic patients, HSA is exposed to high concentrations of glucose over extended periods of …

Screening For Chloroplast Inner Envelope-Thylakoid Membrane Contact Site Proteins, Evan W. Labrant

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Most life on Earth is dependent upon the capture of solar energy and subsequent fixation of carbon. In members of the Archaeplastida lineage these biological processes take place in semi-autonomous organelles called chloroplasts. Chloroplasts are bounded by a double membrane envelope and contain the photosynthetic membrane system, thylakoid membranes, where light capture takes place. While a great deal is known about how thylakoid lipids are synthesized and protein complexes therein are properly maintained, very little is known regarding the processes by which lipids are transported to thylakoids which lack de novo glycerolipid synthesis. We have worked to identify candidate proteins …

Treating The Black Fever: Evaluating Combination Chemotherapy For Leishmania Donovani, Robert Frank Mickatavage

Biochemistry and Molecular Biology

Visceral leishmaniasis (VL) is a neglected tropical disease (NTD) endemic to Africa, Asia, and the Americas, caused by the parasite L. donovani and spread by the Phlebotomine sandfly. If left untreated, VL is almost always fatal, bearing a mortality rate of over 95%. Many individuals within endemic regions are often too poor to afford treatment, and the financial burden of current treatments may only exacerbate their poverty. Antimonials and more modern treatments display varying effectiveness, but are nonetheless toxic to the host, commonly inducing hepatotoxicity, nephrotoxicity, and renal failure. The development of more effective and safer treatments is crucial, particularly …

Sodium And Potassium In Health And Cellular Function, Jordyn Branz

Honors Program: Senior Projects (Public)

Sodium (Na⁺) and potassium (K⁺) are essential electrolytes that regulate numerous physiological processes. These include cell function, nerve transmission, and muscle contraction. The Na+/K+-ATPase plays a critical role in maintaining the balance of these ions by actively transporting three sodium ions out of the cell and two potassium ions into the cell against their concentration gradients. This process is vital for maintaining the resting membrane potential and supporting the function of excitable cells. The Na+/K+-ATPase consists of two main subunits, with the alpha-subunit being primarily responsible for ion transport activity. Isoforms alpha1, alpha2, and alpha3 are tissue-specific and contribute to …

Identification Of Cadmium As A Structural And Functional Modulator Of Psd-95 Regulating Nmdars At Postsynaptic Membranes, Claudia Garza

Theses and Dissertations

Postsynaptic density-95 (PSD-95) is an essential scaffolding protein in excitatory neurons. PSD-95’s N-terminal palmitoylation region elicits synaptic plasticity by targeting, anchoring, and trafficking glutamate receptors, such as N-methyl-d-aspartate receptors (NMDAR), to the postsynaptic membrane. The molecular interactions of PSD-95 and its dysregulation in excitatory synapses are currently being explored as primary causes of neurodegenerative diseases and disorders, such as Alzheimer’s disease, Schizophrenia, and Parkinson’s disease. Recent studies demonstrate an overaccumulation of zinc at two cysteines (C3 and C5) and two histidines (H24 and H28) of PSD-95 blocks palmitoylation, causing a loss of NMDAR at the postsynaptic membrane. In addition, exposure …

Effects Of Cholesterol Concentration On Liposome And Proteoliposome Behavior, Ehsaneh Khodadadi

Graduate Theses and Dissertations

Cholesterol is crucial in modulating the behavior and characteristics of biological membranes, liposomes, and proteoliposomes, for instance in drug delivery applications. Cholesterol regulates membrane stability by influencing lipid density, phase separation, and protein-membrane interactions. In planar bilayers, cholesterol enhances membrane thickness, reduces permeability, and promotes lipid ordering, adding rigidity and fluidity. Cholesterol also modulates membrane curvature in curved bilayers and vesicles, stabilizing low-curvature regions. In this work, all-atom molecular dynamics (MD) simulations were employed to examine how varying cholesterol concentrations influence the structure and dynamics of membranes, focusing on planar and curved geometries. Bilayers with cholesterol molar ratios of 0%, …

The Regulatory Role Of Collagen Α1(Xi) Amino-Terminal Domain Isoforms In Collagen Fibrillogenesis, Abu Sayeed Chowdhury

Boise State University Theses and Dissertations

Collagen α1(XI) is a minor fibrillar collagen involved in the critical regulation of collagen fibrils, such as nucleation, assembly, and regulation of fibril diameter. The amino-terminal domain consists of an amino-propeptide (Npp) domain and a variable region, which is the result of alternative splicing from exon 6A, 6B, 7, and 9. The spliced variants involving Npp, with the combinations of exon 6A, 6B, 7, and 9 gives rise to different isoforms with very distinctive chemical nature. The Npp of collagen α1(XI) chain is retained on the surface of the collagen fibril for an extended period of time and may play …

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 …

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 …

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 …