Biochemistry, Biophysics, and Structural Biology Commons^™

Using The Safety Scissors: Dna Resection Regulation At Dna Double-Strand Breaks And Telomeres, Michael M, Soniat, Logan R. Myler

Department of Biochemistry and Molecular Biology Faculty Papers

DNA resection is a universal process in genome maintenance by which one strand of DNA is degraded, leaving the other strand intact. This sometimes highly processive process is critical for many forms of DNA damage repair, replication-coupled repair, meiotic recombination, and telomere maintenance. Therefore, resection must be tightly regulated to prevent genome instability and promote faithful and accurate repair. Here, we review what is known about how resection functions and how it is controlled, using DNA double-strand break repair and telomere maintenance as examples. We address how resection is regulated in three independent steps: resection initiation, long-range processing, and termination. …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Identification Of Serum Exosome Proteins In Systemic Sclerosis With Interstitial Lung Disease By Aptamer Proteomics, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A major unmet need for Systemic Sclerosis (SSc) clinical management is the absence of well validated biomarkers for early diagnosis of SSc-associated interstitial lung disease (SSc-ILD). The objective of this study was to identify proteins contained within serum exosomes that may serve as potential biomarkers to differentiate patients with Diffuse SSc without SSc-ILD from patients with Diffuse SSc with SSc-ILD employing aptamer-based proteomics.

METHODS: Serum exosomes were isolated from two cohorts of patients. The first cohort included 15 patients with Diffuse SSc without SSc-ILD and 14 patients with Diffuse SSc with SSc-ILD and the second cohort included 12 patients …

Biocomputing Approach To Modeling And Modulating Calcium Signaling, Sehee Sun

School of Computing: Dissertations, Theses, and Student Research

Biocomputing is an emerging field that seeks to perform computational tasks using biological substrates and processes. Unlike conventional computing systems based on silicon hardware, biocomputing leverages the parallelism, energy efficiency, and complex dynamics of living systems. Among various cellular mechanisms, calcium (Ca2+) signaling stands out as a central regulator of diverse biological functions, offering a promising basis for programmable logic and control in living cells.

This thesis introduces a novel framework for modeling and modulating Ca2+ dynamics using biologically inspired Boolean logic circuits. Specifically, we propose the Ca2+ Boolean Logic (CaBL) model, in which Ca2+ fluxes and interactions are abstracted …

Synthesis Of Carboxymethyl Cellulose From Nypa Fruticans For Coating Metformin On Zn-Based Metal-Organic Framework Nanohybrid As A Bionanocomposite Drug Delivery System, Delviani Delviani, Viola Giary Rizkillah Maharani, Putri Nur Shadrina, Tri Warni, Regina Wan Azizah, Indra Lasmana Tarigan, Madyawati Latief

Makara Journal of Science

Diabetes is a common and rapidly spreading disease that affects 6.6% of the world’s population. Metformin hydrochloride (HCl) is an effective oral pharmacological treatment for type 2 diabetes mellitus (T2DM) patients because of its capability to reduce glucose levels and the risk of hypoglycaemia. However, gastrointestinal sensitivities to this drug can cause diarrhoea, nausea, vomiting and stomach ache. An alternative is controlled release technology by coating metformin with carboxymethyl cellulose (CMC) and zinc-metal-organic framework (Zn-MOF) through the encapsulation method. Therefore, this study aimed to coat metformin formulations using CMC in a Zn-MOF to control release into the body and minimise …

Microscopic Nucleic Acid-To-Protein Ratio: A Label-Free Approach For Pancreatic Cancer Detection, Sky Gao, Keerthi Priya Jangili, Alfred Akinlalu, Emmanuel Ogberefor, Tommy Gao, Kalpana Devaraj, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

Accurate and timely diagnosis remains a major clinical challenge, hindered by the limitations of conventional histopathological methods, which often rely on labor-intensive staining protocols and subjective interpretation by specialized pathologists. These methods can fail to capture the full molecular and phenotypic heterogeneity of tumors, leading to increased diagnostic time, cost, and variability. To overcome these challenges, we developed a novel label-free ultraviolet (UV) microscopic imaging technique that exploits the intrinsic optical absorption properties of cellular nucleic acids and proteins. By modifying standard brightfield microscopes, our approach quantitatively measures the nucleic acid-to-protein ratio (NPr), enabling high-resolution visualization and discrimination between malignant …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed

Maaen Journal for Medical Sciences

Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …

Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg²⁺ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg²⁺ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …

Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …

Detection And Quantification Of Total Airborne Fungi And Coccidioides Species In Environmental Samples, Theresa T. Roehr

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fungal exposure can cause acute and chronic illnesses or exacerbate existing illnesses. Some fungi are opportunistic pathogens and can lead to serious systemic fungal infections. In 2020, more than 150 million cases of severe fungal infections were reported globally resulting in an estimated 1.7 million deaths. Coccidioidomycosis, or Valley fever, is classified as a serious fungal infection caused by the fungi Coccidioides immitis and C. posadasii. These particular fungi are prevalent in the soil of the Southwestern United States, including Las Vegas, Nevada. In 2024, there were a total of 269 cases of Valley fever reported in Nevada, and …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

Investigating The Effect Of Fasting On Senescent Cells In Nothobranchius Furzeri Fish, Israel A. Akinola

Electronic Theses and Dissertations

Senescent cells (SCs) have been documented to accumulate with age in the organism. Recent studies have shown that reducing the number of SCs in an organism result in tissue rejuvenation and extension of life expectancy. Intermittent fasting is reported to have multiple health benefits and is speculated to reduce the burden of SCs. Nothobranchius furzeri are a new model organism for studying aging and for which there are short- and long-lived strains available. We hypothesize that long- and short-lived strains of N. furzeri will accumulate SCs at different rates; and that fasting will reduce the burden of SCs.

The results …

Exploring The Role Of Lysine Acetylation During Biofilm Formation In Bacillus Subtilis, Jennifer Nguyen, Briana Ericka Reid, Valerie Carabetta

Rowan-Virtua Research Day

Biofilms are structured communities of bacterial cells encased in a self-produced extracellular matrix, composed of polysaccharides, extracellular DNA, and proteins. Bacteria in a biofilm pose significant challenges in healthcare due to their resistance to disinfectants and tolerance to antibiotics. In some species, histone-like proteins were found to be important structural components of the biofilm. Nε-Lysine acetylation is a widespread post-translational modification (PTM) in bacteria, which can alter a protein’s function. The histone-like protein HBsu in Bacillus subtilis is acetylated at seven sites in vivo. We hypothesized that the acetylation state of HBsu may alter biofilm structure or the genetic programming, …

Exploring Intracellular Signaling Responses To Ks18, A Potent Mcl-1 Inhibitor, In Multiple Myeloma, Emily Nelson, Omar S Al-Odat, Dhruti A. Brahmbhatt, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Kumar Pandey

Rowan-Virtua Research Day

Multiple myeloma (MM), a cancer of plasma B cells, is a hematological malignancy in which patients inevitably relapse and develop drug resistance. Mcl-1, a member of the anti-apoptotic subgroup of Bcl-2 family proteins, plays a critical role in the progression of multiple myeloma and contributes significantly to drug resistance. Elevated Mcl-1 expression is observed in approximately 52% of MM patients at diagnosis, increasing to 81% at relapse. Given its driving role in disease progression and therapy resistance, Mcl-1 inhibition has emerged as a promising therapeutic target, prompting ongoing research into the development and clinical evaluation of Mcl-1 inhibitors, particularly for …

Antiproliferative Effects Of Salvia On Breast Cancers., Allison C. Portaro

College of Arts & Sciences Senior Theses

Breast cancer is the most common cancer diagnosed in female adults, with 2.3 million new cases worldwide in 2020. Plants have been used in traditional medicine and are a potential source of pharmaceuticals. One example is the large Lamiaceae (mint) family. The Salvia genus, commonly known as the sages, is the largest genus in Lamiaceae with almost 900 known species. Salvia lyrata (lyre-leaved sage) has a history of Native American medicinal use to treat cancers and other ailments resulting in this plant being referred to as ‘cancer weed.’ Extracts were produced from the leaves of S. lyrata, S. lyrata …

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 …

Direct Synthesis Of Cerium Oxide Nanoparticles In Reducing Sugars: Enhanced Ce3+ Surface Density For Biological Application, Balaashwin Babu, Elayaraja Kolanthai, Craig J. Neal, Samarah V. Harb, Udit Kumar, Yifei Fu, Sudipta Seal

Rowan-Virtua Research Day

Cerium oxide nanoparticles (CNPs) are recognized for their ability to scavenge reactive oxygen species (ROS), making them promising candidates for mitigating oxidative damage in biomedical applications. However, many conventional synthesis methods limit the formation of Ce³⁺ states, which are critical for this antioxidant function. Building upon previous findings that glucose can promote Ce³⁺ formation, this study investigates the broader impact of both reducing (glucose, fructose, galactose) and non-reducing (dextran, sucrose, cyclodextrin) natural sugars on CNP synthesis. CNPs were synthesized in the presence of these sugars, and the surface densities of Ce³⁺ were measured. Results showed that reducing sugars significantly increased …

Hypoxia Induced Ribosomal Rna Fragmentation Mediated By Rnase L, Vanessa Kristina Pizutelli, Dimitri G Pestov

Rowan-Virtua Research Day

Ischemic injury contributes to a range of global pathologies. Ischemia/Reperfusion Injury (IRI) is a paradoxical phenomenon that involves an initial restriction of blood flow followed by a sudden restoration of perfusion. This type of injury takes place in conditions such as myocardial infarction, acute kidney disease, and ischemic stroke and often leads to cellular death. Additionally, IRI exacerbates post-surgical outcomes and plays a role in graft dysfunction and transplant rejection. Despite efforts to develop therapies targeting known IRI pathways, clinical trials have largely been unsuccessful, underscoring the need for alternative mechanisms and biomarkers associated with IRI-induced apoptosis. Reactive oxygen species …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

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 …

Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu

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

Horizontal gene transfer (HGT) via natural competence allows bacteria to incorporate extracellular DNA (eDNA) into their genomes, facilitating genetic diversity and adaptation. In Acinetobacter species, natural competence depends on DNA binding and uptake mediated by type IV pili (T4P). T4P are dynamic extracellular filaments composed primarily of the major pilin subunit PilA, along with a few minor subunits. T4P drive a range of cellular functions including twitching motility, biofilm formation, and DNA uptake, with some functions dependent on pilus retraction and others not. However, how Acinetobacter T4P bind DNA and how T4P/eDNA interactions impact biofilm formation remain unclear. Here, I …

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 …

Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim

Open Access Theses & Dissertations

In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …

Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais

Open Access Theses & Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and complex malignancy that accounts for 15% of pediatric acute lymphoblastic leukemia (ALL) cases in the United States. Tyrosine kinases control critical cellular processes, including the development, survival, and activation of T cells, and are established drivers of leukemia.Tyrosine kinases involved in hematological disorders include receptor tyrosine kinases and non-receptor tyrosine kinases family members such as SRC, ABL, FAK, and Janus kinases (JAKs). This study primarily focused on JAK1 gain-of-function (GoF) mutations. These mutations are recognized as hyperactivating mutations, maintaining kinase activity of JAKs on and essentially keeping downstream signaling effectors, like …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

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 …