Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing.

The Human Silencing Hub (HuSH) complex is composed of TASOR, MPP8, and PPHLN1 subunits and serves as a conserved protein complex responsible for silencing transposable elements in vertebrate animals. Despite its importance, the regulatory mechanisms and recruitment dynamics governing this complex remain poorly understood. In this study, we have identified a second HuSH complex, termed HuSH2, centered around TASOR2, a paralog of the core TASOR protein in HuSH. Our findings indicate that every subunit in both HuSH and HuSH2 has an important role in achieving precise genomic localization to distinct, non-overlapping genomic loci. We utilized in silico protein structure prediction to simulate the interactions between MPP8 and both TASOR paralogs. Drawing on the insights gained from these predictions, we implemented amino acid substitutions that interfered with the binding of MPP8 to each HuSH complex. Leveraging these MPP8 transgenes and other constructs, we identified an important role played by the relative quantities of HuSH complexes in controlling the activity of LINE-1 elements. Furthermore, our results suggest that dynamic changes in TASOR and TASOR2 expression enable cells to finely tune the extent of HuSH-mediated silencing. Our study provides insights into the intricate interplay between HuSH complexes, illuminating their important role in the regulation of retrotransposon silencing.

Rethinking the Difficult Patient: Formative Qualitative Study Using Participatory Theater to Improve Physician-Patient Communication in Rheumatology.

BACKGROUND: Effective physician-patient communication is crucial for positive health outcomes for patients with chronic diseases. However, current methods of physician education in communication are often insufficient to help physicians understand how patients' actions are influenced by the contexts within which they live. An arts-based participatory theater approach can provide the necessary health equity framing to address this deficiency. OBJECTIVE: The aim of this study was to develop, pilot, and conduct a formative evaluation of an interactive arts-based communication skills intervention for graduate-level medical trainees grounded in a narrative representative of the experience of patients with systemic lupus erythematosus. METHODS: We hypothesized that the delivery of interactive communication modules through a participatory theater approach would lead to changes in both attitudes and the capacity to act on those attitudes among participants in 4 conceptual categories related to patient communication (understanding social determinants of health, expressing empathy, shared decision-making, and concordance). We developed a participatory, arts-based intervention to pilot this conceptual framework with the intended audience (rheumatology trainees). The intervention was delivered through routine educational conferences at a single institution. We conducted a formative evaluation by collecting qualitative focus group feedback to evaluate the implementation of the modules. RESULTS: Our formative data suggest that the participatory theater approach and the design of the modules added value to the participants' learning experience by facilitating interconnection of the 4 communication concepts (eg, participants were able to gain insight into both what physicians and patients were thinking about on the same topic). Participants also provided several suggestions for improving the intervention such as ensuring that the didactic material had more active engagement and considering additional ways to acknowledge real-world constraints (eg, limited time with patients) in implementing communication strategies. CONCLUSIONS: Our findings from this formative evaluation of communication modules suggest that participatory theater is an effective method for framing physician education with a health equity lens, although considerations in the realms of functional demands of health care providers and use of structural competency as a framing concept are needed. The integration of social and structural contexts into the delivery of this communication skills intervention may be important for the uptake of these skills by intervention participants. Participatory theater provided an opportunity for dynamic interactivity among participants and facilitated greater engagement with the communication module content.

Harnessing Split-Inteins as a Tool for the Selective Modification of Surface Receptors in Live Cells.

Biochemical studies of integral membrane proteins are often hampered by low purification yields and technical limitations such as aggregation causing in vitro manipulations to be challenging. The ability of controlling proteins in live cells bypasses these limitations while broadening the scope of accessible questions owing to the proteins being in their native environment. Here we take advantage of the intein biorthogonality to mammalian systems, site specificity, fast kinetics, and auto-processing nature as an attractive option for modifying surface proteins. Using EGFR as a model, we demonstrate that the split-intein pair AvaN /NpuC can be used to efficiently and specifically modify target membrane proteins with a synthetic adduct for downstream live cell application.

Say Something, Do Something: Evaluating a Forum Theater Production to Activate Youth Violence Prevention Strategies in Schools.

BACKGROUND: Youth violence that takes place within school settings exposes youth to serious social, mental and physical consequences that affect education performance, and life opportunities. Previous work shows positive youth development frameworks can promote social-emotional learning by enhancing empathy and building problem-solving and conflict management skills. Theater-based interventions have been shown to enhance social emotional development by privileging youth voices, and building youth capacities and strengths. The current manuscript presents the evaluation of an arts-based and public health framework conducted to assess the development, implementation and impact of a forum theater production, Say Something, Do Something (SSDS) in St. Louis, Missouri. METHODS: An iterative mixed methods approach was used, starting with observations of productions. Using convenience sampling, we then conducted post interviews of the theater team (n = 8) and school personnel (n = 10). RESULTS: Respondents highlighted that as a result of engagement of school personnel in program development, the language and scenarios presented were relevant to students. Data indicated that SSDS increased student knowledge and changed attitudes, developed student conflict management and problem-solving skills, and improved interpersonal behavior. SSDS also raised awareness of the importance of, and created the foundation for, additional system and policy changes in the schools. CONCLUSION AND IMPLICATIONS: Forum theater is an approach that can enhance socio-emotional learning and conflict management among youth. Collaborative initiatives between public health and the arts are poised to uniquely engage community partners, animate interventions, and impact critical public health issues including youth violence prevention.

Molecular basis for DNA recognition by the maternal pioneer transcription factor FoxH1.

Forkhead box H1 (FoxH1) is an essential maternal pioneer factor during embryonic development that binds to specific GG/GT-containing DNA target sequences. Here we have determined high-resolution structures of three FoxH1 proteins (from human, frog and fish species) and four DNAs to clarify the way in which FoxH1 binds to these sites. We found that the protein-DNA interactions extend to both the minor and major DNA grooves and are thus almost twice as extensive as those of other FOX family members. Moreover, we identified two specific amino acid changes in FoxH1 that allowed the recognition of GG/GT motifs. Consistent with the pioneer factor activity of FoxH1, we found that its affinity for nucleosomal DNA is even higher than for linear DNA fragments. The structures reported herein illustrate how FoxH1 binding to distinct DNA sites provides specificity and avoids cross-regulation by other FOX proteins that also operate during the maternal-zygotic transition and select canonical forkhead sites.

Students for others: Correlates of adherence to COVID-19 guidelines.

Objective: The present study aimed to determine correlates of adherence to COVID-19 health precautions among college students. Drawing from the literature, the following constructs were considered: self-efficacy, conscientiousness, social support, collectivism, empathy, and fear of COVID. Participants: Undergraduate students (N = 92) recruited from psychology classes and social media, living on and off-campus, served as participants during fall 2020. Methods: Participants completed a short self-report survey, delivered online, measuring adherence to COVID-19 health precautions and its possible correlates. Results: After preliminary comparisons showing no differences in adherence between students living on and off-campus, linear regression analyses of the complete sample revealed that the significant predictors of adherence were conscientiousness, collectivism, empathy, and fear of COVID. Conclusions: College student adherence was largely driven by interpersonal motivators coupled with a modest level of fear, rather than more general constructs. These findings offer implications for considering targets in public health campaigns delivered to college students.

Acceleration of mobile health for monitoring post-transplant in the COVID-19 era: Applications for pediatric settings.

BACKGROUND: Since the start of the COVID-19 pandemic and consequent lockdowns, the use of telehealth interventions has rapidly increased both in the general population and among transplant recipients. Among pediatric transplant recipients, this most frequently takes the form of interventions on mobile devices, or mHealth, such as remote visits via video chat or phone, phone-based monitoring, and mobile apps. Telehealth interventions may offer the opportunity to provide care that minimizes many of the barriers of in-person care. METHODS: The present review followed the PRISMA guidelines. Sources up until October 2020 were initially identified through searches of PsycInfo® and PubMed® . RESULTS: We identified ten papers that reported findings from adult interventions and five studies based in pediatrics. Eight of the adult publications stemmed from the same two trials; within the pediatric subset, this was the case for two papers. Studies that have looked at mHealth interventions have found high acceptability rates over the short run, but there is a general lack of data on long-term use. CONCLUSIONS: The literature surrounding pediatric trials specifically is sparse with all findings referencing interventions that are in early stages of development, ranging from field tests to small feasibility trials. The lack of research highlights the need for a multi-center RCT that utilizes robust measures of medication adherence and other outcome variables, with longer-term follow-up before telehealth interventions should be fully embraced.