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Ignite the Spark: A Multi-State Collaboration for Engaging and Retaining 4-H Volunteers
No full textVolunteers are critical to 4-H program delivery; however, volunteer retention remains a persistent challenge within youth development organizations. To address this concern, a coalition of 4-H volunteer specialists from the Southern region designed and delivered a five-part webinar series titled Ignite the Spark: Strategies for Engaging and Retaining 4-H Volunteers. This series provided professional development on volunteer engagement and retention for 4-H youth development professionals across the United States. Topics included personal and program readiness, recruitment, engagement, and retention strategies. More than 450 extension professionals from 12 states participated in the live sessions, with an additional 228 completing asynchronous, self-paced modules. Evaluation data indicated significant knowledge gains among participants in key areas such as Personal Readiness (4.7/5), and volunteer engagement (4.5/5). The initiative’s success demonstrates the effectiveness of regional collaboration in developing comprehensive, research-based professional development resources. This program practice offers a promising blueprint for future endeavors to integrate resources and knowledge to empower volunteer-led programs and address the critical issue of volunteer retention in youth development organizations
Multiscale 3D Whole Joint Cellular and Molecular Mapping Reveals Disease-Specific Neurovascular Plasticity Underlying the Structure-Pain Relationship
No full textUnderstanding musculoskeletal joints from a 3D multiscale perspective, from molecular to anatomical levels, is essential for resolving the confounding relationships between structure and pain, elucidating mechanisms regulating joint health and diseases, and developing new treatment strategies. Here, a musculoskeletal joint immunostaining and clearing (MUSIC) method specifically developed to overcome key challenges of immunostaining and optical clearing of intact joints are introduced. Coupled with large-field light sheet microscopy, this approach achieves 3D high-resolution, microscale neurovascular mapping within the context of whole-joint anatomy without the need for image coregistration across various joints, including temporomandibular joints, knees, and spines, and multiple species, including mouse, rat, and pig. These results reveal 3D heterogeneous neurovascular distributions and previously uncharacterized neurovascular pathways within joints. Using two complementary models of joint disease, degeneration and injury, disease-specific microscale neurovascular alterations are identified. These findings extend beyond conventional macroscale assessments of joint morphology and provide a framework to link structural changes with pain. Importantly, our results show that the relationship between joint structure and pain is not universal but disease-dependent, underscoring distinct pain mechanisms in different disease contexts. This platform offers a powerful tool for multiscale 3D analysis, advancing understanding of joint pathophysiology and intricate interplay among joint tissues
4. Assignment Three: Scopes Trial Introductory Assigned Activities: Learning from Tennessee’s Scopes Trial 100 Years Later
No full textThis assignment encourages students to engage actively with scaffolded pre-learning necessary for the Scopes Trial unit. Students are introduced to the history of the 1925 Scopes Trial and the folk history connected to Inherit the Wind, in its various forms
Ex Vivo Multiplex Knockdown of ANGPTL3 and Cypor in Hepatocytes as a Novel Cell Therapy for Familial Hypercholesterolemia
No full textInherited metabolic diseases (IMDs) affect approximately 1 in 800 individuals. The only curative treatment for IMDs is liver transplantation. However, transplantation carries significant risks, including organ rejection and a lifelong need for immunosuppression. Therefore, gene editing has emerged as a promising alternative to liver transplantation for treating IMDs.
Familial hypercholesterolemia (FH) is and IMD characterized by elevated LDL-C levels resulting in premature cardiovascular disease. CRISPR-Cas9-mediated gene editing to disrupt the gene encoding angiopoietin-like 3 (ANGPTL3) in the liver represents a novel therapeutic approach for FH. Nonviral delivery performed ex vivo is safer than systemic delivery because gene editing is in only the intended target cell type. However, low engraftment by gene-edited hepatocytes poses a challenge. Knocking down NADPH-cytochrome P450 oxidoreductase (CYPOR), followed by treatment with APAP, can potentially increase engraftment by gene-edited cells in the liver after transplantation. Our cell-based gene-editing strategy for treating FH involves isolating hepatocytes from the patient, editing hepatocytes ex vivo with CRISPR-Cas to knockdown ANGPTL3 and CYPOR, transplanting the gene-edited cells back into the patient, followed by transient APAP administration to select edited cells in the liver.
Results from this study indicate that combining APAP selection with electroporation is a promising gene editing strategy for treating FH. This research also shows that it is possible to treat a wide array of inherited metabolic liver diseases for which there are no preexisting selective advantages for gene-edited hepatocytes by disrupting Cypor in combination with a therapeutic target via electroporation-mediated, multiplex gene editing followed by APAP selection
Development of Mixed O/S-Donor Imidazole Thione Ligands for Trivalent Lanthanide/Actinide Separations
Get PDFSeparation of lanthanides and actinides is difficult due to their very similar size and charge. Increasing selectivity for actinides over lanthanides is possible by incorporating a softer, more polarizable donor atom into a chelating ligand, since the softer donor atom is capable of greater orbital overlap with the 5f orbitals of the actinides vs the 4f orbitals of the lanthanides. Sulfur-containing imidazole thione chelating ligands have not been investigated for this purpose but possess a resonance structure that puts significant negative charge on the sulfur, enabling it to form strong metal-sulfur bonds compared to other sulfur-containing ligands such as thioethers and thiophenes. Addition of electron-withdrawing substituents on the imidazole nitrogens permits tuning of the ligand electronics. However, traditional basic conditions for synthesis of imidazole thiones do not work for the target acetate and propionate substituents, since the substituent arm is more readily deprotonated than the imidazole ring. Tang et al. reported a synthesis of imidazole thiones without the use of basic conditions that they proposed went through a radical addition of sulfur to imidazole. Investigation of this sulfur addition mechanism uncovered temperature and reagent concerns that led to the development of a new and simplified synthetic pathway for substituted imidazole thiones. The mechanism for sulfur addition to the imidazole ring is nucleophilic aromatic substitution rather than the radical mechanism reported by Tang et al. Understanding this new mechanism allows a significant broadening of the synthetic scope for these compounds. Utilizing our newly synthesized, mixed O/S-donor imidazole thione ligands, we performed liquid-liquid extractions, to determine their actinide vs lanthanide selectivity using 241Am and 152Eu. We compared our extraction results with these imidazole thione ligands with results from a commercially available thiophene ligand to determine the viability of the thione functional group for these applications. All the ligands demonstrated metal coordination, but significant selectivity was only observed for one of the tested thiones. To determine the radiolytic stability of imidazole thiones, 1H NMR spectroscopy was used to determine the concentration of intact thione in samples subjected to gamma irradiation. Increased radiolytic stability was observed for the imidazole thiones containing electron-withdrawing substituents. These studies demonstrate that tuning the electronics of these ligands can enhance radiolytic stability and impacts how the thione functional group can be further explored in the development of selective and radiolytically robust ligands for trivalent actinide and lanthanide separations