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CHARACTERIZATION OF P38alpha AND NITRIC OXIDE SYNTHASE 3 BINDING
P38alpha is a member of the mitogen activated protein kinase (MAPK) family. This family is important for mediating signal transduction pathways through phosphorylation of downstream substrates. Previous work has described the ability of p38alpha to bind and phosphorylate nitric oxide synthase 3 (NOS3) at two sites, the autoinhibitory loop (AI) at S600 and the N-terminal MAPK binding site (NtMAP) at S114. P38alpha has two substrate binding domains, the common docking groove (CD-groove) and a hydrophobic pocket (DEF) that are important in binding and phosphorylating various substrates specific to each pocket. Utilizing biolayer interferometry, this work describes the importance of both pockets in binding NOS3. AI peptides preferentially bound an interfering DEF pocket variant of p38alpha suggesting the CD-groove is important for binding whereas NtMAP peptides preferentially bound an interfering CD-groove variant, demonstrating reliance on DEF pocket binding. Phosphorylation of p38alpha (WT and variants) at the activation loop demonstrated an overall better affinity to NOS3 peptides. Oxidation of p38alpha induces a disulfide bond in the CD-groove and we found an increase in affinity to the NtMAP, suggesting binding of the disulfide form is mediated through the DEF pocket. Overall, NOS3 phosphorylation at S114 and S600 is DEF pocket dependent. NOS3 and p38 binding in situ detected with proximity ligation assay revealed localization of phosphorylated S114 to the nucleus in HMEC-1 cells. All together these findings provide insight into the complex interactions of binding and activity leading to new questions about the impact in regulation of NOS3 and p38
Comparative Analysis of Phyllosphere Microbiota in American and Chinese Wild Type Chestnuts as well as Their Hybrids
The American chestnut, Castanea dentata, was once a dominant tree species in the forests of eastern North America until it was deemed functionally extinct due to the fungus, Cryphonectria parasitica, that caused the chestnut blight. Restoration efforts have been underway to restore the tree to its native range using backcross breeding with the Chinese chestnut, Castanea mollissima. Hybridized species are bred to retain morphological characteristics of the American chestnut but include blight resistance of the Chinese genotype. Although a few studies have examined leaf characteristics such as stomatal density and leaf mass per area (LMA) in wild-type and hybrid trees, no known studies have characterized their phyllosphere communities, and only a limited number have investigated leaf decomposition and heterotrophic respiration of senesced leaves. With the potential for hybrid reintroduction, it is important to understand how hybrid leaf characteristics, microbiomes, and decomposition compares to those of the wild-type American counterpart, and whether hybrids could occupy the same ecological niche. A three-part study was conducted to examine leaf characteristics, bacterial and fungal microbial communities, and heterotrophic respiration of the leaves from American, Chinese, and two hybrid genotypes of chestnuts. It was hypothesized that phyllosphere communities and heterotrophic respiration rates would differ between American, Chinese, and hybrid genotypes. It was also hypothesized that leaf morphology and genetic makeup of American chestnut trees are better predictors of phyllosphere microbial species diversity and community composition than location. To test these predictions, leaves from American, Chinese, and hybrid (B3 and B3F3) trees were collected from two orchard locations. Leaf Mass Area and stomatal densities were measured, DNA extractions were performed, and a heterotrophic respiration study was conducted. Results showed that microbiome communities did differ among genotypes. Leaf characteristics were not indicative of phyllosphere differences, but genotype, and to a lesser extent, location, were. Heterotrophic respiration differed in one hybrid species (B3F3). Overall, results suggest that hybrid chestnut leaf morphology and microbiomes more closely resemble American genotypes than Chinese genotypes. These findings are promising for reintroduction efforts, but additional research is needed
Anatomy of a Purple State: A North Carolina Politics Primer
Christopher A. Cooper Chapel Hill: University of North Carolina Press, 2024 ISBN: 9781469681719 216 p. $22.00 (Pbk
Teacher Leadership in Social Studies: The Search for Meaning and Identity
This qualitative research study brings together social studies education and teacher leadership. Social studies lacks study in the teacher leader literature. This study aimed to understand whether the disciplinary nature of social studies education influenced the enactment of teacher leadership. This study sought an answer to the central research question: What does it mean to be a social studies teacher leader? Using a hermeneutic phenomenology research design, data were collected through semi-structured interviews across two groups of participants. Seven social studies teacher leaders made up one group, and five social studies teachers without leadership roles comprised the other. Findings indicated that social studies teacher leaders experience teacher leadership in a manner similar to teacher leaders in other disciplines. Emergent findings suggest that when social studies teacher leaders apply the perspectives and principles of social studies education, it can inform their approach to enacting teacher leadership. Furthermore, social studies teachers and leaders balance multiple role identities, such as “coach,” well when a dynamic systems model is applied to their understanding. This study fills a gap in the teacher leader literature by demonstrating that social studies as a discipline can inform teacher leadership. The findings suggest that more emphasis should be placed by teachers, school and district-level leaders, and educational policymakers on professional learning surrounding teacher leadership and the perspectives and principles of social studies education
Molecular Visualization Laboratory (BIOL4450): Molecular Visualization of Phosphoethanolamine Methyltransferase from Plasmodium falciparum
Malaria is a major worldwide health threat as this disease, caused by different species of Plasmodium parasites, results in over 1 million deaths and 300 million clinical cases each year. Due to the large negative impacts which Malaria has on humanity, it is important to research and identify novel biochemical pathways that avoid drug resistance. One such pathway that has potential to highlight specific drug targets is the phosphobase methylation pathway which synthesizes phosphocholine, a precursor of phosphatidylcholine. A key enzyme of this pathway, specific to Plasmodium falciparum, is the phosphoethanolamine methyltransferase (PfPMT) enzyme which is responsible for sequential methylation reactions. PfPMT holds a unique 3D structure when compared to its other forms found in plants and protists making it a novel target for drug development. Specifically, the conformation of PfPMT in complexed with phosphoethanolamine (pEA) and S-adenosylhomocysteine (SAH) provides insights into the structure and function of its active site. In the Molecular Visualization Laboratory (BIOL4450) class at KSU, to gain a better understanding of the PfPMT 3D structure, biochemical methods such as site-directed mutagenesis and protein purification were used to perform X-ray crystallography. Additionally, X-ray crystallography experiments were conducted as a vital source to collect information on the 3D structures of PMT and interactions with ligands. Finally, the 3D structure of PfPMT was visualized and analyzed using a series of tools, including virtual reality (VR), augmented reality (AR), and 3D printing, to contribute to the field of STEAM (science, technology, engineering, art, and math) and improve academic understanding of protein biochemistry. Through use of biochemical techniques and direct analysis of 3D visualization methods of PMT will contribute to a greater understanding of its active site function and structure. With new insights on PMT 3D structure and function, novel drug approaches may be developed in the future
Integrated Treatment and Suicide Prevention in Healthcare Facilities
Abstract
This study examines the relationship between the provision of integrated mental health and substance use treatment, and suicide prevention services in healthcare facilities. The key research question asks, “Is there a connection between offering integrated mental health and substance use treatment and the likelihood of a facility providing suicide prevention services?” The hypothesis suggests that facilities offering integrated care are more likely to provide suicide prevention services due to the increased vulnerability of clients with dual diagnoses.
Data from the National Substance Use and Mental Health Services Survey (N-SUMHSS) is used to analyze this relationship. The primary variables are whether a facility offers integrated mental health and substance use treatment, and whether it provides suicide prevention services. Additional factors include the percentage of clients with dual diagnoses, the provision of mental health treatment to both substance use, and non-substance use clients, and whether the facility offers case management services.
This research addresses an urgent public health issue—the intersection of mental health, substance use, and suicide prevention. By identifying service provision patterns, the study aims to inform more effective interventions for vulnerable populations. It is expected that facilities offering integrated care will also provide suicide prevention services, highlighting the importance of such models in addressing complex healthcare needs.
The study’s findings could inform future research on how integrated care models impact client outcomes, such as reduced substance use and suicide risk. Further exploration of facility characteristics, like staff training and resource availability, may enhance the effectiveness of these interventions. This research contributes to public health strategies by suggesting that integrated care models may improve long-term outcomes for at-risk groups through more comprehensive service provision
The Effects of Inappropriate Inheritance of Histone Methylation on Muscle Structure and Function
At fertilization, maternally deposited histone modifying enzymes establish germline versus somatic transcriptional states by adding and removing histone methylation. To do this in C. elegans, the H3K4 demethylase, SPR-5, removes active H3K4 methylation, while the H3K9 methyltransferase, MET-2, adds repressive H3K9 methylation to prevent germline gene expression in the soma. Recent studies show that SPR-5; MET-2 maternal reprogramming is antagonized by the H3K36 methyltransferase, MES-4, which maintains H3K36 methylation at germline genes to ensure proper germline gene expression in germ cells. Maternal loss of SPR-5 and MET-2 allows MES-4 to maintain H3K36 methylation at germline genes in the soma leading to ectopic expression of germline genes and developmental phenotypes including muscle defects. Here, we show that muscle morphology and function are compromised in spr-5, met-2 mutants, but can be rescued by knocking down MES-4. We also show that late generation spr-5 and met-2 single mutants display increased muscle disorganization that does not correlate with decreased motility. Together, our data provide insights into how mis inherited histone methylation affects muscle function
BMI vs Diabetes
One of the most pressing public health concerns in the U.S. has been how “obesity has been associated with an increased risk of several chronic diseases, including type 2 diabetes.” Obesity can cause diabetes often linked to chronic conditions such as high blood pressure and heart disease. The study conducted utilizes data from the CDC’s 2015 Behavioral Risk Factor Surveillance Survey (BRFSS), to explore the relationship between Body Mass Index (BMI) and diabetes rate. The primary goal of the CDC’s data is to determine whether the Body Mass Index has a significantly relevant relationship with the probability of developing diabetes. The study hypothesizes that individuals with diabetes have a higher BMI. Additionally, it will be evaluated that secondary variables—such as high blood pressure, high cholesterol, age, heart disease, and physical activity, will either contribute to or modify this association. Specifically, individuals with diabetes and conditions like high blood pressure or heart disease, are predicted to show a higher BMI. The BRFSS contained over 70,000 observations on variables such as age, BMI, physical activity, high blood pressure, and diabetes status. Both continuous and categorical data were analyzed using statistical methods to assess the relationship between these variables. Following the hypothesis, it’s anticipated that the results will show a positive association between higher BMI, diabetes, and the secondary variables diagnosis, aligning with previous research linking obesity to diseases such as hypertension, and cancers. The results of the study could lead to valuable conclusions about strategies targeting obesity and lowering BMIs to reduce the risk of diabetes. With this study, it could address methods to reduce BMI to lower the risk of other chronic conditions as well