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The Effects of Increased Oligomannose N-Glycan Expression on Neuroblastoma Progression and Epidermal Growth Factor Receptor Signaling
No full textN-glycosylation is an essential post-translational modification with known roles in cancer, including the pediatric cancer neuroblastoma (NB). The folding, stability, regulation, and trafficking of proteins are all dependent on proper N-glycosylation. There are three general classes of N-glycans: oligomannose, hybrid, and complex ranging from the least processed to the most respectively. Changes in metabolism, endoplasmic reticulum (ER) stress, and other cell signaling events can and do exert influence on the N-glycosylation processing pathway to ensure all glycoproteins are processed to fit the current needs of the cell. Pathological diseases are known to exert influence on the types of N-glycans produced. Regarding cancer biology, β1,6 complex N-glycans have often been attributed to the malignant transformation of cells. This work seeks to define the types of N-glycans (oligomannose, hybrid, or complex) that contribute to the progression of neuroblastoma.
The link between N-glycosylation and the malignant transformation of cells has often been centered around more processed N-glycans (i.e., complex N-glycans). However, in the body of this work, we find that oligomannose N-glycans are responsible for aggressive neuroblastoma phenotypes, mainly increased invasiveness. By CRISPR/Cas9 knockout of MGAT1, MGAT2, or MGAT3 in human and rat neuroblastoma cell lines, we were able to generate cells with varying levels of N-glycan processing of proteins. MGAT1 encodes N-acetylglucosaminyltransferase-I (GnT-I), a critical glycosyltransferase that converts oligomannose N-glycans to hybrid N-glycans. By loss of GnT-I, cells have reduced synthesis of hybrid N-glycans and therefore also reduced production of complex N-glycans, resulting in cells with increases in oligomannose N-glycan content. MGAT2 encodes GnT-II, which converts hybrid N-glycans to complex N-glycans. Loss of GnT-II prevents the synthesis of complex N-glycans resulting in cells enriched with hybrid N-glycan structures. MGAT3 encodes GnT-III, which produces bisecting hybrid and complex N-glycans and is responsible for terminating N-glycan processing. By knockout of GnT-III, hybrid and complex N-glycans should be more susceptible to additional modifications (e.g., fucosylation, sialylation, galactosylation, etc.). With these various cell lines, we were able to explore how the reduced amounts of various N-glycan modifications influenced neuroblastoma growth, invasion, and cell-cell adhesion; ultimately revealing that increased expression of oligomannose N-glycans leads to neuroblastoma cells that are highly invasive but have decreased proliferation. Furthermore, we examined unmodified human neuroblastoma cells derived from a SK-N-BE(2) cells: BE(2)-C and BE(2)-M17. We found that BE(2)-M17 cells expressed more oligomannose N-glycans and were significantly more invasive but less proliferative relative to BE(2)-C cells, furthering the support that oligomannose N-glycans drive neuroblastoma invasiveness. These studies were instrumental in designating oligomannose N-glycans as perpetrators of aggressive neuroblastoma phenotypes.
A primary focus of this work was to better understand how oligomannose N-glycans impacted neuroblastoma progression. Neuroblastoma cells expressing high amounts of oligomannose N-glycans exhibit increased invasiveness but decreased proliferation leading us to examine intracellular signaling, specifically the oncogenic receptor tyrosine kinase, epidermal growth factor receptor (EGFR). Knockout of MGAT1 is a powerful approach to enrich all N-glycosylated proteins of cells with oligomannose N-glycans, including EGFR. This investigation builds upon the towering literature surrounding N-glycosylation and EGFR, in particular how N-glycosylation modification of EGFR impacts the receptor’s ability to initiate downstream signaling. The 12-13 N-glycans of EGFR have been characterized as being mostly complex N-glycans and have been shown to be essential to both EGFR’s function and regulation; however, very few have attempted to examine how EGFR functions when decorated primarily with oligomannose N-glycans. Here we show BE(2)-C(-MGAT1) cells produce oligomannosylated EGFR (EGFR decorated with oligomannose N-glycans). Further characterization of oligomannosylated EGFR revealed that ligand independent phosphorylation and EGF stimulated phosphorylation are significantly increased in BE(2)-C(-MGAT1) cells. Furthermore, when observing proliferation in response to EGF stimulation in 3D conditions, BE(2)-C cells do not have a major proliferate response whereas BE(2)-C(-MGAT1) cells proliferate robustly likely due to the heightened EGFR phosphorylation of oligomannosylated EGFR. The increased autophosphorylation and sensitization of BE(2)-C to EGF stimulation when expressing oligomannosylated EGFR, due to loss of MGAT1, is novel and further details how changes in N-glycosylation, due to a pathogenic state, could alter a cellular phenotype without genetic mutation in EGFR.
Here using both rat and human neuroblastoma cells with selective defects in the N-glycan processing of proteins we further define the role of N-glycosylation in the progression of neuroblastoma. By examining various N-glycosylation mutations as well as unmodified neuroblastoma cell lines we were able to establish that oligomannose N-glycans contribute to neuroblastoma progression through heightened invasiveness. Utilizing newly generated BE(2)-C(-MGAT1) cells we further explored the role of oligomannose N-glycans by examining EGFR signaling in BE(2)-C and BE(2)-C(-MGAT1) cells. Neuroblastoma cells bearing oligomannosylated EGFR respond intensely to EGF stimulation, leading to heightened autophosphorylation and EGF stimulated proliferation. Ultimately, we conclude that neuroblastoma cells with increased oligomannose N-glycan content is consistent with a highly invasive cancer that is readily able to undergo EGF stimulated proliferation
Exploring Systemic Medical Traumatic Stress In Historically Marginalized Patients
No full textHistorically marginalized patients are at an increased risk for healthcare experiences that increase their risk for adverse health events, adverse health outcomes, and psychological distress related to medical trauma. These factors are exacerbated by experiences of structural violence through discrimination and microaggressions. However, research that describes the unique distress historically marginalized patients’ experience related to medical trauma, adverse health events, adverse health outcomes, and structural violence is sparse in healthcare literature. This study seeks to bridge this gap by exploring the interplay between factors and how they each contribute to patients’ experiences. This research is informed by the biopsychosocial-spiritual framework (BPSS) and historical trauma theory, which considers how collective trauma shared by historically marginalized patients spans multiple generations, affects the biopsychosocial-spiritual health of the group, and may result in trauma-related symptoms.
Medical trauma, resulting from adverse health events and adverse health outcomes, is a critical yet understudied aspect of healthcare experiences, particularly among historically marginalized populations. This quantitative research, with a national sample, sheds light on the complexities of the relationship between the psychological distress resulting from medical trauma among such groups while recognizing the profound implications in shaping their healthcare. Through a comprehensive examination of the interplay between adverse health events, adverse health outcomes, social determinants of health, structural violence, internal stress, health care policies, practices and procedures, and medical trauma this study elucidates the mechanisms underlying a new concept explored within this dissertation described as systemic medical traumatic stress and its role within historically marginalized communities
The Influence of Policy on School Nursing Practice
No full textIntroduction/Significance: School nurses are in an optimal position to influence the health of a
large population of school-age children. Literature suggests that school nursing practice varies greatly, and school nurse interventions are often focused on various priorities of school
health. Policy implementation in schools that include school nurse intervention may facilitate an increase in specific school nurse practice. This case study examined the school nurse practice and school policy dyad of one school nurse in a rural area of North Carolina.
Methods: Case study design was used to examine the practice of a unique case of a school nurse in a rural area of North Carolina and associated school policy. Secondary data generated from a de-identified school nurse interview was the primary source of evidence. Two additional sources of evidence were used, the school health website for the school district and the school’s policy related to school nutrition. The data were analyzed to identify similarities between the school nurse’s practice and related school policy. Results: One overarching theme was identified, 1) Inclusion of the school nurse in policy facilitated school nurse practice, and one subtheme was identified 1) Communication, school nurse awareness of existing policy and communication is vital. Findings indicated that the school nurse’s practice in this case was directly influenced by the presence of a related school policy and the school nurse's awareness of the policy. Both the school health website and the school policy reviewed integrated the role of the school nurse. Discussion: While the findings of this case study are not generalizable to all school nurses, findings support the impact on practice with the inclusion of the school nurse in policy and the school nurse's awareness of school policy
UNDERAPPRECIATED AND OVERWHELMED: ADDRESSING TEACHER BURNOUT AND SELF-EFFICACY THROUGH THE USE OF A SOCIAL AND EMOTIONAL PROFESSIONAL LEARNING FRAMEWORK.
No full textRecognizing that feelings of being overworked, undervalued, and isolated contribute significantly to teacher burnout—leading to increased absenteeism and attrition—this inquiry explored the implementation of a teacher-focused SEL professional learning framework to help mitigate these negative effects. By fostering social-emotional competence through consistent training and support, teachers can create a more positive classroom climate that enhances student outcomes. Utilizing an explanatory sequential mixed methods research design grounded in improvement science, this inquiry measured teacher absences and self-efficacy following the professional learning program’s implementation. Additionally, qualitative insights were gathered from teachers’ experiences regarding job satisfaction and retention. The findings reveal that while the SEL framework positively impacted teachers' sense of belonging and support, contributing to a slight reduction in burnout levels and absenteeism, deeper structural issues persist. Teachers reported ongoing challenges related to work-life balance and low self-efficacy in critical areas, such as classroom management and parent engagement.
The findings also underscore the complexity of addressing teacher burnout and highlight the need for a multifaceted approach that combines social-emotional interventions with targeted professional development. Educational leaders are urged to develop strategies that specifically enhance teachers’ confidence and competencies, ultimately fostering a more supportive and effective learning environment. This inquiry provides critical insights into the dynamics of teacher well-being and offers a foundation for future research and practice aimed at improving teacher retention and student outcomes. Lastly, the findings highlight the interplay between teacher well-being and student outcomes, emphasizing that addressing teacher burnout through SEL not only enhances teachers' emotional health but also fosters a positive classroom environment conducive to student learning. For practitioners, implications of this inquiry include the need for implementing comprehensive support systems and targeted professional development to sustain teacher efficacy and retention, ultimately leading to improved educational experiences for both teachers and students
Towards Automated Garment Measurements In the Wild Using Landmark and Depth Estimation
No full textThis research introduces an innovative approach to automate garment measurements from photos, combining depth estimation and landmark detection to address the high return rates in the fashion industry due to inaccurate sizing. Utilizing the DeepFashion2 dataset and a custom set of images, we employ DepthAnything for depth estimation and Keypoint R-CNN for landmark estimation, advancing previous methodologies by offering a scalable and accurate solution for the fashion industry. Initial findings suggest promising avenues for reducing returns and enhancing the garment fitting processes
Evaluation of MagicSchool AI-Generated Elementary Teaching Materials: A Self-Study
No full textRecent developments in Artificial Intelligence (AI) have resulted in many possible tools, such as MagicSchool AI, that educators could use in their practice. Possible outcomes of using AI in their practice could be reduced teacher burnout, reduced time for developing materials, and increased time for other aspects of their role as an educator. Thus, the purpose of this mixed methods self-study is to investigate my experiences using MagicSchool AI to generate elementary classroom materials for a two-week integrated instructional unit, the quality of the AI-generated materials, and my pedagogical decisions surrounding using those materials in my personal teaching practices. I collected the following data: AI-generated lesson plans, lesson materials, and assessments; evaluation of AI-generated materials; personal journal entries; and recorded and transcribed critical friend conversations. Quantitative data analysis included descriptive statistics, and qualitative data analysis included open coding and axial coding to identify themes. The findings address experiences utilizing MagicSchool AI to generate classroom materials, professional development opportunities, best AI practices for using in the elementary classroom, and my pedagogical decisions based on the quality of the materials. Implications for future practice are discussed for pre-service and in-service teachers as they use AI to generate classroom materials and future research
Cooperation vs. Competition in Teams in the Business Environment
No full textBalancing cooperation and competition in the business environments is essential to fostering productive team dynamics and high performance. This research study examines how various factors including demographics (age, gender), employment status, personal styles, educational background field of study/industry, trust, monetary rewards, online environments, in-person environments, time working with an individual, and relationships relate with an individual’s inclination to either cooperate or compete in team environments. Many factors relate to understanding if an individual is cooperative or competitive but there also are mixed-motive situations (Levi, 2017). By analyzing data from a survey, classroom activity, interviews, and secondary research I concluded findings of cooperation vs. competition in business environments relating to students and business professionals
Determining the Usability of a Web-Based Intervention for Bereaved Parents
No full textThe death of a child is a traumatic experience that can put parents at risk for adverse mental and physical health effects such as cardiac illnesses, prolonged grief disorder, anxiety, and depression. This research project aims to determine the overall feasibility, usability and acceptability of a virtual bereavement intervention called ADAPT. ADAPT is a fully online bereavement tool that provides parents and siblings with personalized resources, professional contacts, and health assessments. This tool was evaluated by collecting research with both healthcare providers and bereaved parents. Interviews with providers and bereaved parents were conducted, in addition to surveys that allowed for analysis of ADAPT and its acceptability and benefit. The goal of ADAPT is to provide a personalized approach to address parental bereavement with a potential to mitigate negative health outcomes. The results of this study indicated that ADAPT is a needed, accessible, and acceptable intervention for bereaved parents
PERI-IMPLANT ACTIVITY RESTRICTION IN CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE PATIENTS: DOES ACTIVITY RESTRICTION RESULT IN LONG-TERM RATES OF LOW-LEVEL ACTIVITY IN PATIENTS?
No full textCardiovascular implantable electronic devices (CIEDs), specifically implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds) are life-saving devices utilized to care for patients at risk for sudden cardiac arrest. ICDs and CRT-Ds have become increasingly used worldwide and within the United States (US), with over 110,000 devices implanted every year in the US (Green et al., 2016). The implantation procedure for the ICD and CRT-D limits patients from engaging in activities that require using their arm or lifting heavy objects from 4-6 weeks post-implant. Physical activity is limited to allow the implanted leads time to become fibrosed. Regardless, cardiac patients need to return to physical activity for both its physical and mental benefits. The resumption of activity following this time is likely variable, but no published information is available to determine the impact or duration of physical activity restriction. Importantly, all modern ICDs and CRT-Ds have an accelerometer in the device that can continuously monitor patient movement and physical activity and store the data.
Research has consistently highlighted that physical activity is a predictor of cardiovascular outcomes and patients’ quality of life, specifically in individuals with CIEDs (Rosman et al., 2018). Given that many of these patients already struggle with engagement in physical activity, coupled with the adjustment to a new device and recovery restrictions, it is plausible that this may impact their levels of activity. Additionally, many patients endure an increase in psychological stressors post-implantation, such as a fear of shocks which may also contribute to a reduction in activity consequently impacting their quality of life (Sears et al., 2023). Changes in health status may also impact patients’ activity levels such as new-onset atrial fibrillation, atrial tachycardia, or ICD shock experiences. Lastly, given the high incidence of cardiovascular disease and decreased resources within rural areas, this may result in lower levels of physical activity (Turecamo et al., 2023). The combination of recovery restrictions, psychological factors, rurality, and the onset of symptoms may create a burden on patients that influences their engagement in physical activity in turn, impacting their long-term cardiovascular outcomes.
The present study aimed to determine how peri-implant activity restrictions within ICD and CRT-D patients seen in a rural-serving cardiology clinic impact long-term rates of activity engagement for up to 6 months post procedure. 294 patients from ECU Health who have a Biotronik ICD or CRT-D device that were in the archival data set from 2014 to 2023 were included in the study. Descriptive analyses revealed that the mean age of the sample was 61.76 (SD = 12.29) with 67.79% identifying as male and 52.04% identifying their racial/ethnic background as non-Hispanic Black. Pre-existing cardiac and psychological co-morbidities prior to device implantation were common within the sample and the majority of the sample received their device due to heart failure (79.93%). Major findings of the present study included a) plateaued activity levels after two months following device implantation (95.90 minutes per day in month 1 and 116.93 minutes per day in month 2) b) no significant difference in activity levels between patients with device detected atrial arrhythmias vs. patients without arrhythmias and c) no significant difference in activity levels between patients who experienced defibrillator shocks vs. patients who had not. The findings in the present study demonstrated decreased physical activity patterns up to 6 months following implantation in a rural-serving clinic. In the future, device and accelerometer data should be utilized for research and to determine mechanisms of utilization to provide interventions, improve patient care, patient quality of life, and overall health outcomes
A Tale of Two Communities: Grave Markers as Illustrations of Marginalization and Self-Determination in African American Cemeteries in Eastern North Carolina
Get PDFBurial practices have long been understood to vary both temporally and culturally. However, little research has been conducted using cemetery trends to compare contemporary historic African American cemeteries in different communities. Ayden and Princeville are two towns in Eastern North Carolina separated by only thirty-five miles and the Tar River. Despite the towns’ proximity, their stories are vastly different. Ayden has been home to both white and African American individuals, often separated by social and economic divisions. Princeville was founded by previously enslaved African Americans who had flocked to the relative safety of a Union Army encampment and is the oldest continually occupied town in the United States founded by African Americans. Though they are similar in size today, both communities have historically existed in very different environments. This research, by comparing trends in gravemarker construction and design, shows how these patterns can represent unique aspects of communities that may otherwise be missed