Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential

CD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4+ T cells impact follicular helper T (TFH) cell versus non-TFH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4+ T cell chromatin landscapes that ultimately shape their effector potential

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

The Hazel Green Academy Revitalization Project

The Hazel Green Academy Revitalization Project is a community service-based project focused around restoring and repurposing the Hazel Green Academy (HGA). HGA was a private, college preparatory high school in Wolfe County, KY, that opened in 1880. At its height, HGA served not only as a school, but also as a source of education and community events. However, HGA closed in 1983 due to a rise in public schools in the area. The HGA Revitalization Project has three strategic priorities: create a community engagement event called Music on the Green; place all campus buildings on the National Register of Historic Places; and use the administration building for educational outreach by holding college courses on HGA’s campus. These strategic priorities will serve the community socially, academically, and holistically as HGA once did. Service-learning projects have been conducted to achieve the three strategic priorities. Students from the Craft Academy at Morehead State University have taken service-learning trips to HGA to maintain campus upkeep. This special project offers students the opportunity to engage in STEM education as well as serve the community. It is the hope of the HGA Revitalization Project to share this innovative project with other STEM-focused students throughout the state of Kentucky and beyond

Self-Reported Cognitive Decline: Differentiating The Worried Well From True Cases

Presentation documenting the differences between normal, age-related changes in memory and thinking versus cognitive change that might be associated with diseases such as Alzheimer’s or dementia. Understanding these age-related changes is important, especially in an era of continual medical advancement that has resulted in an increase of our elderly population. Cognition changes in normal-aging adults typically results in slower, less accurate decision-making or processing external stimuli at a slower rate. Age-related diseases such as Alzheimer’s accelerates the decline in neuronal functioning and, consequently, cognitive decline which has a detrimental impact on the individual’s ability to perform activities of daily living. Participants of the study were selected by the study coordinator and the Director for the Center for Excellence in Aging & Health. Study research teams were made up of a variety of health professionals including social workers, pharmacists, and occupation therapists. We interviewed participants, gathered health histories, and administered a cognitive screening battery. We utilized the preliminary results to select certain participants to complete a Phase II interview process. We plan to analyze the data as a whole and will leverage our findings to not only assist those who are True Cases to find a path to proper treatment but to advance our knowledge of normal cognitive aging and other changes associated with true cognitive diseases.https://dune.une.edu/cecespring2021/1009/thumbnail.jp

Biopsychosocial Dimensions Of Chronic Pain Care

Presentation describing the following: Pain management and proper care for patients with chronic pain, from a student perspective, is initially conceptualized as a concern relating to physical health and well-being. Healthcare students receive education on the importance of holistic practice and the impacts of biopsychosocial dimensions of health on wellbeing. However, when entering a situation with the anticipation to treat chronic pain our immediate concern was providing care for physical ailments. As time went on, the importance of psychological, mental health care became increasingly evident as important to help best treat our patients. In this presentation, we will be discussing our experience with the IPE Pain Clinic and the experience’s impact on our understanding of the Biopsychosocial aspects of health that all heavily influence the health and well-being of our patients both current and future.https://dune.une.edu/cecespring2021/1014/thumbnail.jp

The Interface between Cell Signaling Pathways and Pregnane X Receptor

Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity