Explicit Content

Duration: 11:35https://digitalcommons.library.uab.edu/ethnographic/1194/thumbnail.jp

Investigating The Role Of Notch1 On Cell Viability In Pancreatic Neuroendocrine Tumor Cells In Hypoxia

INVESTIGATING THE ROLE OF NOTCH1 ON CELL VIABILITY IN PANCREATIC NEUROENDOCRINE TUMOR CELLS IN HYPOXIA ALEXIS KENNEDY MULTIDISCIPLINARY BIOMEDICAL SCIENCE ABSTRACT Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms originating from neuroendocrine cells in the pancreas. Patients with advanced disease pose a complex challenge due to poor prognosis and limited treatment options. Notch signaling is a juxtracrine cell-cell communication mechanism whereby transmembrane Notch receptors (Notch 1-4) interact with neighboring cells through ligands binding, resulting in a cascade that regulates various developmental processes and cell fate decisions. Dysregulated Notch1 signaling is implicated in PNETs, affecting neuroendocrine tumor biology and potentially interacting with Hypoxia Inducible Factor (HIF) pathways in disease progression. We hypothesized Notch1 in PNET cells provides a survival advantage in hypoxia. The PNET cell line BON-1 and derivative Notch1 Knockout (N1KO) cells were grown under normoxic (21% O2) or hypoxic conditions (3% O2). N1KO was achieved using CRISPR-Cas9. Cellular viability was measured with MTT and CellTiter-Glo (CTG) viability assays, and apoptosis was analyzed by flow cytometry with Annexin V/7-AAD staining. HIF-2α expression was determined by immunofluorescence and immunohistochemistry after hypoxia. Statistical analysis was performed using t-tests in Microsoft Excel. After 48 hours of hypoxia exposure, CTG assay showed BON-1 cells maintained 84% +/- 10% viability, while N1KO cells showed 73% +/- 14% (p=0.04). In a 48h MTT assay, BON-1 cells exhibited increased viability of 110% +/- 5%, while N1KO viability dropped to 80% +/- 9% (p\u3c0.001). Both lines had reduced viability at 72 hours, with a greater reduction in N1KO cells (BON-1: 52% +/- 14%, N1KO: 37% +/- 11%, p \u3c 0.05). Flow cytometry revealed increased apoptosis and necrosis in both cell lines under hypoxia, with BON-1 showing higher survival than N1KO. Immunohistochemistry revealed increased nuclear expression of HIF-2α and HIF-1α in N1KO cells under normoxia, which was further confirmed by immunofluorescence. These findings demonstrate Notch1’s role in regulating cellular responses to hypoxia, influencing viability, apoptosis, and necrosis. The differential responses of BON-1 and N1KO cells suggest Notch1 promotes PNET cell survival under low oxygen and balances apoptosis and necrosis. Future studies should explore how Notch1 interacts with cell survival and metabolism regulators, potentially guiding therapeutic strategies for patients with PNETs

Warm-water Fish Gelatin Nanofibers Produced via Alternating Field Electrospinning

2025 Spring Expo Poster Presentation Works in Progresshttps://digitalcommons.library.uab.edu/sp-expo/1086/thumbnail.jp

Identifying differentiation markers between dermal fibroblasts and adipose-derived mesenchymal stromal cells (AD-MSCs) in human visceral and subcutaneous tissues using single-cell transcriptomics (additional file 3)

Supplementary Material

Synergistic Effects Of Hyaluronic Acid And Mechanical Strain On Ovarian Cancer Cell Behaviors

Ovarian cancer is the most lethal gynecological cancer, but despite this, the effects of the ovarian tumor microenvironment (TME) on disease progression are poorly understood. The TME consist of the extra cellular matrix (ECM), cellular components, and mechanical forces. Cancer associated fibroblasts (CAFs) are stromal cells that secrete several ECM components including collagen, fibronectin, and hyaluronic acid (HA). CAFs also have increased motility and contractility, this increased movement creates micro-strains experienced by the tumor cells in the TME. HA interacts with cancer cells as both a serum and stromal component. Increases in stromal HA in the ovarian TME are associated with a more progressed disease state and a worse 5-year survival rate, but serum HA does not have these same correlations. HA influences cancer cell behaviors through cell surface receptor CD44. The intracellular domain of CD44 interacts with Src which links CD44 to oncogenic pathways including MAPK, PI3K, and Rho/Roc. Through these mechanisms, the HA/CD44 signaling axis alters ovarian cancer cell proliferation, invasion, and drug resistance. It is known that Src is mechanically sensitive but the mechanism in which HA plays a role in this sensitivity is not well characterized. We hypothesize that tension through HA in the ovarian TME alters CD44 signaling and further downstream functional outcomes. In a 2D platform we modeled the combined effects of tensile strain and serum or stromal HA. We evaluated altered CD44 and downstream Src expression and expanded our studies into a complex microphysiological system that allowed us to evaluate how combined strain and stromal-like HA alter CD44 functional effects including proliferation, migration, and response to chemotherapy treatment. Our results show that a stromal-like HA presentation works synergistically with tensile strain to increase CD44 expression and increase pro-cancer cellular behaviors. These results highlight the importance of including not only biochemical but also biomechanical factors when modeling ovarian cancer. Our findings help elucidate the role of the TME in disease progression and gives valuable insight for potential therapeutics that target the HA/CD44 axis

An Examination Of Psycho-Behavioral Risk And Resilence Profiles In People With Chronically Painful Knee Osteoarthritis

The prevalence and impact of chronic pain are far-reaching and costly to our society. Chronic pain conditions are affecting many people in the US and abroad. Osteoarthritis (OA) is commonly referred to as a slow progressing degenerative disease that tends to develop over 10 to 15 years and can result in functional limitations and pain. Chronic knee OA is a common form of OA pain that affects many adults across the globe. Biopsychosocial factors are theorized to play an important role in how people with chronic pain may develop, exacerbate, or cope with pain. The goal of this project was to investigate the relationships between psycho-behavioral risk, resilience, and their combined profiles as a predictive marker of pain and functioning as assessed by self-report and functional movement tasks. Data were collected from people with knee OA in one or both knees (n = 211) across two sites: University of Alabama at Birmingham, and University of Florida, Gainesville. Among the sample, 65.9 % were female, 54.5 % identified as Non-Hispanic Black (NHB), 62.6 % collected at UAB and the mean age was 61.0 (SD = 8.78). Overall, the results indicated that, 1) there are many strong relationships within psycho-behavioral risk/resilience measures for people with chronic knee OA, 2) a combined psycho-behavioral risk and resilience profile can be used to extract the most essential components of these measures using a PCA, 3) clustering methods based on the most important overall extracted components are useful for creating a data driven approach to generating profiles of varying psycho-behavioral risk/resilience, and 4) that these profiles show differences on important aspects of the chronic pain experience such as self-reported recall of pain on questionnaires, pain evoked from movement, and functional ability score on a series of movements. This research provides insight into the biopsychosocial model of chronic pain that is necessary for moving the field of pain research and treatment forward

Optical absorption of defects in aluminum nitride

Aluminum nitride (AlN) is an ultrawide bandgap semiconductor material known for its applications in high power microelectronic and optoelectronic devices due to its high thermal conductivity and high electrical resistivity. Point defects are known to hinder the material’s properties and are therefore a subject of interest in semiconductor materials research. The samples used in this work were grown by physical vapor transport (PVT) at Hexatech and they exhibit amber and clear coloration as well as a nonuniformity of charge, which was investigated. Experiments were carried out by electron paramagnetic resonance (EPR) and photo-EPR spectroscopy in order to detect the defect and determine its ionization energy. Simulations of the EPR signal were performed to determine a g-value of g║ = 2.001 and a hyperfine value of 3.8 mT which are consistent with literature reports and hyperfine calculations, which identify the defect as a carbon on a nitrogen site, CN. Photo-EPR results determined that the threshold for photo-excitation occurs at approximately 4 eV and peaking at 4.7 eV, which is consistent with the reported 4.7 eV absorption attributed to carbon. A threshold for photo-quenching occurs at approximately 2 eV. The charge state transition of a negative to neutral CN-/0 then was found to occur at approximately 2 eV above the valence band maximum, Ev, which is in agreement with theoretical predictions for CN. Analysis of EPR results revealed the cause to possibly be a concentration-dependent donor-acceptor-pair recombination between a donor and a compensating carbon. This work reveals the mechanism for the electronic processes involved in this AlN material

Exploring Gaps In Hiv Prevention: Hiv Pre-Exposure Prophylaxis Awareness, Attitudes, Utilization, Coverage, Hiv Testing And Risk Perception Among Sub-Saharan African College Students In The United States

This dissertation focuses on increasing HIV awareness and contributing to efforts at reducing new HIV infections among Sub-Saharan African (SSA) college students. It begins with an introductory chapter one and ends in the concluding chapter five. Chapter two presents a systematic review identifying key gaps in HIV Pre-Exposure Prophylaxis (PrEP) knowledge, attitudes, and utilization among Black college students in the United States (U.S). The review synthesizes findings from four studies, revealing that a third of participants demonstrated adequate PrEP knowledge, while PrEP utilization remained under-utilized at three percent. Key barriers to PrEP uptake included fear, low self-perceived HIV risk, infrequent HIV testing, and reliance on inaccurate information sources such as social media. To address these gaps, the chapter emphasizes targeted educational interventions that address both individual and structural barriers to improve PrEP awareness, attitudes, and uptake, ultimately advancing sexual health outcomes in this high-risk population. Chapter three focuses on a concept analysis review of HIV PrEP coverage among Black adults in the U.S. Based on eleven selected studies, the review identifies four distinct definitions of HIV PrEP coverage, highlighting significant racial disparities in PrEP access and utilization. Despite Black individuals being a high-priority population for HIV prevention, they continue to experience disproportionately higher rates of new infections. Through a comprehensive concept analysis, the chapter proposes a unified definition of PrEP coverage that emphasizes equitable access and identifies key attributes, antecedents, and consequences of PrEP use. The findings underscore the need for improved policies, tailored access strategies, and consistent communication to mitigate health inequities and support national HIV prevention goals. Chapter four presents a qualitative phenomenological study exploring HIV PrEP awareness, testing behaviors, and risk perception among SSA college students in the U.S., a subgroup of Black college students that has been understudied. Findings indicate that only 32.8% perceived themselves at HIV risk, 22.7% had ever tested for HIV, and 68.2% were unaware of PrEP. Themes emerging from participant experiences highlight psycho-social factors, socio-cultural influences, facilitators of PrEP awareness and testing engagement. The chapter offers a foundational perspective on improving sexual health outcomes for SSA college students in the U.S