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Aim: Recovery of damaged mucosal surfaces following inflammatory insult requires diverse regenerative mechanisms that remain poorly defined. Previously, we demonstrated that the reparative actions of Trefoil Factor 3 (TFF3) depend upon the enigmatic receptor, leucine rich repeat and immunoglobulin-like domain containing nogo receptor 2 (LINGO2). This study examined the related orphan receptor LINGO3 in the context of intestinal tissue damage to determine whether LINGO family members are generally important for mucosal wound healing and maintenance of the intestinal stem cell (ISC) compartment needed for turnover of mucosal epithelium.Methods and Results: We find that LINGO3 is broadly expressed on human enterocytes and sparsely on discrete cells within the crypt niche, that contains ISCs. Loss of function studies indicate that LINGO3 is involved in recovery of normal intestinal architecture following dextran sodium sulfate (DSS)-induced colitis, and that LINGO3 is needed for therapeutic action of the long acting TFF2 fusion protein (TFF2-Fc), including a number of signaling pathways critical for cell proliferation and wound repair. LINGO3-TFF2 protein-protein interactions were relatively weak however and LINGO3 was only partially responsible for TFF2 induced MAPK signaling suggesting additional un-identified components of a receptor complex. However, deficiency in either TFF2 or LINGO3 abrogated budding/growth of intestinal organoids and reduced expression of the intestinal ISC gene leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), indicating homologous roles for these proteins in tissue regeneration, possibly via regulation of ISCs in the crypt niche.Conclusion: We propose that LINGO3 serves a previously unappreciated role in promoting mucosal wound healing.

Here, we present a 10-week project-oriented laboratory module designed to provide a course-based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically-relevant human enzyme, protein tyrosine phosphatase 1B (PTP1B). Over the course of the semester students guide their own mutant of PTP1B from conception to characterization in a cost-effective manner and gain exposure to fundamental techniques in biochemistry, including site-directed DNA mutagenesis, bacterial recombinant protein expression, affinity column purification, protein quantitation, SDS-PAGE, and enzyme kinetics. This project-based approach allows an instructor to simulate a research setting and prepare students for productive research beyond the classroom. Potential modifications to expand or contract this module are also provided.

Background: Despite advances in HIV treatment, gaps in care retention threaten the individual health of people with HIV (people) and public health efforts to end the HIV epidemic., Objective: This project aimed to identify and address gaps in retention and support re-engagement in care., Methods: A multipronged initiative at five community HIV clinics and community-based organizations (CBOs) included patient, healthcare professional (HCP), and community-focused interventions. Patient-oriented interventions included instructional videos for patients to view before appointments and conversation guides about barriers to care for patients to use with staff during appointments. HCP-oriented interventions included baseline surveys assessing clinic practices and challenges and audit-feedback sessions to review survey findings and devise plans to improve retention strategies. Community-oriented interventions included education sessions co-led by clinics and CBOs, micro-learning engagements at community events, and social media campaigns covering topics related to HIV care. Data were collected through surveys administered before and after patient- and HCP-oriented interventions and community education sessions, follow-up surveys administered after micro-learning engagements, and reach of social media campaigns., Results: Patient-oriented interventions led to improvements in patient-reported empowerment and confidence in their ability to remain in care. HCPs also reported improvements in patient intake and follow-up processes after audit-feedback sessions. Community interventions reached over 1,000 community members combined, with education sessions and micro-learning engagements uncovering key barriers to HIV care and leading to improvements in knowledge and awareness of local HIV services., Conclusion: This multipronged initiative demonstrates how patient, HCP, and community-oriented education can support retention and re-engagement in care.