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mir-276a Is Required for Muscle Development in Drosophila and Regulates the FGF Receptor Heartless During the Migration of Nascent Myotubes in the Testis
Full text linkMicroRNAs function as post-transcriptional regulators in gene expression and control a broad range of biological processes in metazoans. The formation of multinucleated muscles is essential for locomotion, growth, and muscle repair. microRNAs have also emerged as important regulators for muscle development and function. In order to identify new microRNAs required for muscle formation, we have performed a large microRNA overexpression screen. We screened for defects during embryonic and adult muscle formation. Here, we describe the identification of mir-276a as a regulator for muscle migration during testis formation. The mir-276a overexpression phenotype in testis muscles resembles the loss-of-function phenotype of heartless. A GFP sensor assay reveals that the 3′UTR of heartless is a target of mir-276a. Furthermore, we found that mir-276a is essential for the proper development of indirect flight muscles and describe a method for determining the number of nuclei for each of the six longitudinal muscle fibers (DLMs), which are part of the indirect flight muscles
Comparison of histochemical methods for the analysis of eosinophils and mast cells using a porcine model of eosinophilic esophagitis
Full text linkAccurate identification of eosinophils in tissue sections is required for diagnosis of eosinophilic esophagitis in humans and the assessment of severity of disease in allergy models. The pig may be a good model for sensitization and allergy models due to anatomical, physiological, and immunological similarities to humans. However, comparative studies on histochemical detection of eosinophils in fixed porcine tissue are lacking. Qualitative and quantitative comparisons were performed for six histochemical methods previously reported for eosinophil and mast cell detection in other species. Astra Blue/Vital New Red, Congo Red, Luna, Sirius Red, Toluidine Blue, and modified regressive Hematoxylin & Eosin were applied to formalin-fixed paraffin embedded full-thickness sections of porcine esophagus. Specimens were collected from young, crossbred pigs sensitized to ovalbumin with or without subsequent oral exposure to ovalbumin to produce eosinophilic esophagitis lesions for comparison to non-allergic controls. Ease of eosinophil quantitation was analyzed, and varied by histochemical stain, to determine whether stain selection increased accuracy and efficiency of evaluation. Noticeable differences in color contrast between intracytoplasmic granules, surrounding tissue, and cellular components aided detection and identification of eosinophils and mast cells with Astra Blue/New Vital Red and Toluidine Blue, respectively. For eosinophils, Congo Red and H&E were adequate, while Luna and Sirius Red presented challenges for quantitation. In this case, rapid and reliable characterization of porcine esophageal allergy models was made possible by using Astra Blue/New Vital Red for eosinophils and Toluidine Blue for mast cells
A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein
Full text linkThe membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly1,2. Here we describe the identification of JNJ-9676, a small-molecule inhibitor targeting the coronavirus M protein. JNJ-9676 demonstrates in vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV and sarbecovirus strains from bat and pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), we determined a binding pocket of JNJ-9676 formed by the transmembrane domains of the M protein dimer. Compound binding stabilized the M protein dimer in an altered conformational state between its long and short forms, preventing the release of infectious virus. In a pre-exposure Syrian golden hamster model, JNJ-9676 (25 mg per kg twice per day) showed excellent efficacy, illustrated by a significant reduction in viral load and infectious virus in the lung by 3.5 and 4 log10-transformed RNA copies and 50% tissue culture infective dose (TCID50) per mg lung, respectively. Histopathology scores at this dose were reduced to the baseline. In a post-exposure hamster model, JNJ-9676 was efficacious at 75 mg per kg twice per day even when added at 48 h after infection, when peak viral loads were observed. The M protein is an attractive antiviral target to block coronavirus replication, and JNJ-9676 represents an interesting chemical series towards identifying clinical candidates addressing the current and future coronavirus pandemics
Memory signatures in path curvature of self-avoidant model particles are revealed by time delayed self mutual information
Full text linkEmergent behavior in active systems is a complex byproduct of local, often pairwise, interactions. One such interaction is self-avoidance, which experimentally can arise as a response to self-generated environmental signals; such experiments have inspired non-Markovian mathematical models. In previous work, we set out to find “hallmarks of self-avoidant memory" in a particle model for environmentally responsive swimming droplets. In our analysis, we found that transient self-trapping was a spatial hallmark of the particle’s self-avoidant memory response. The self-trapping results from the combined effects of behaviors at multiple scales: random reorientations, which occur on the diffusion scale, and the self-avoidant memory response, which occurs on the ballistic (and longer) timescales. In this work, we use the path curvature as it encodes the self-trapping response to estimate an “effective memory lifetime" by analyzing the decay of its time-delayed mutual information and subsequently determining the longevity of significant nonlinear correlations. This effective memory lifetime (EML) is longer in systems where the curvature is a product of both self-avoidance and random reorientations as compared to systems without self-avoidance
Accounting for aid: estimating the impact of United States’ global health investments on mortality among women of reproductive age using synthetic control and Bayesian methods
Full text linkBackground: The United States government (USG) is a key global actor in preventing mortality and supporting lifesaving health services among women and children in low- and middle-income countries (LMICs). Since the Foreign Assistance Act of 1961, USG has funded global health programmes targeting specific conditions and strengthening health systems for the delivery of essential services via the United States Agency for International Development (USAID) and other USG agencies. However, directly quantifying and attributing the impact of USG health investments is challenging due to the inability of conducting randomised control trials for such large programmes at scale. In this study, we compared two quasi-experimental impact evaluation approaches to estimate the effects of sustained USG health investments on mortality among women of reproductive age (WRA). Methods: We employed synthetic control analysis and a Bayesian alternative to synthetic control to estimate the impact of USG's global health investments on WRA mortality rate across 16 LMICs that received sustained, multifaceted, and above-average USAID global health funding levels from 2005 to 2019. Results: Countries receiving sustained, multifaceted, and above-average USAID global health funding had a reduction in the annual WRA mortality rate by 0.65 deaths per 1000 WRA throughout the post-treatment period. For the years (i.e. 2009-2019) where the effect estimates are statistically significant (P < 0.001), the reduction in WRA mortality rate was 0.80 deaths per 1000 WRA. Sensitivity analyses and Bayesian modelling supported the robustness of these findings. We conservatively estimated that about 1.0-1.3 million WRA deaths were averted in study countries between 2009 and 2019 as a result of USG health investments. Conclusions: Our results suggest that well-funded donor initiatives can substantially reduce WRA mortality rates beyond what would have been achieved without such investments. Sustained donor investments significantly reduce WRA mortality, underscoring the transformative potential of well-funded global health initiatives. Our study also demonstrates that synthetic control and Bayesian models are valuable tools for evaluating the impact of large-scale global health financing
BRIDGING COMMUNITIES, BOOSTING NUTRITION: ADDRESSING PUBLIC HEALTH THROUGH INFRASTRUCTURE IMPROVEMENTS IN FAYETTEVILLE, NC
Full text linkFayetteville, North Carolina, faces a public health crisis rooted in poor walkability and limited food access, contributing to high rates of obesity, diabetes, and food insecurity—especially among low-income and minority residents. With a Walk Score of 21/100, the city ranks among the least walkable in the U.S. This capstone proposes a place-based nutrition intervention integrating two evidence-based models: the Complete Streets Initiative and Safe Routes to Healthy Food (SRHF). The intervention includes (1) constructing pedestrian and bike infrastructure within a one-mile radius of grocery stores and (2) establishing SRHF corridors to connect food-insecure neighborhoods with retailers. Grounded in the socioecological model, the plan aims to increase physical activity and improve dietary behaviors. Evaluation methods include traffic counts, consumer surveys, dietary recalls, and geospatial analysis. This initiative seeks a 20% increase in foot traffic and a 25% improvement in produce consumption, offering a cost-effective, equity-driven strategy to reduce chronic disease in underserved communities.Master of Public Healt
IMPROVING FOOD ACCESS FOR BLACK RESIDENTS IN UNDERINVESTED AREAS OF GRANVILLE AND VANCE COUNTIES
Full text linkFood insecurity is a systemic issue within the built environment of Granville and Vance (GV) counties, North Carolina (NC), that has pervasive negative effects on residents’ health outcomes. Analysis of GV counties’ built environment identified food insecurity as a priority to address. The team performed contextual analyses to gain comprehensive understanding of the impact food access has on residents, and what factors influence that relationship. As a result, the team identified several recommendations to reduce food insecurity while prioritizing equity-centered, community-driven solutions. Through establishment of a food resource directory, expansion of the NC Department of Transportation’s Microtransit program, and creation of a food insecurity steering committee, access to adequate nutrition would improve for GV counties’ residents. These efforts, in combination with local partnerships and stakeholder collaboration, can reduce barriers to food access and assistance programs. Additionally, these recommendations form a strong foundation for future improvements to be made. Master of Public Healt
Shaping future leaders: developing an MPH leadership curriculum through problem-based learning
Full text linkLeadership is essential to public health practice, yet few MPH programs offer structured, integrated approaches to cultivating leadership competencies. At the University of North Carolina’s Gillings School of Global Public Health, the Leadership in Practice (LIP) MPH concentration responds to this gap by embedding problem-based learning (PBL) throughout a multi-course curriculum designed to prepare students for real-world leadership challenges. Drawing on interdisciplinary faculty expertise and a constructivist pedagogical philosophy, the LIP curriculum emphasizes systems thinking, strategic decision-making, and values-based leadership development. This manuscript describes how PBL is applied across five required courses to help students synthesize technical knowledge with collaborative problem-solving and applied leadership skills. We also present alumni and employer feedback that illustrates the curriculum’s impact on workplace readiness and leadership capacity. This case study offers a model for integrating leadership development into graduate public health education and calls for broader adoption of applied, interdisciplinary pedagogies that prepare students to lead transformative change in diverse public health settings
SARC 2025 ( Highlighting the Need for Research Exploring the Role of Religious Engagement in Mitigating Negative Mental Health Outcomes Among Autistic Older Adults)
Full text linkThis project explores how aging affects individuals with autism, a topic that has received far less attention compared to research on children and adolescents. The study investigates challenges related to mental health, daily living, and social support in autistic adults, while also highlighting gaps in existing research and services. By analyzing current literature, the project identifies patterns of increased mental health concerns, limited access to resources, and the need for better support systems as autistic individuals age. These findings emphasize the importance of addressing aging in autism research to improve long-term quality of life and guide future clinical and policy efforts.