A mixed-methods investigation of COVID-19 pandemic-specific stress in college students.

OBJECTIVE: To identify pandemic-specific stressors among college students and compare patterns of stressors in samples obtained during early and chronic phases of the pandemic. METHOD: Different undergraduate student samples from a Southeastern university completed an online survey in Spring 2020 (early pandemic; N = 673) and Fall 2020 (chronic pandemic; N = 439). This repeated cross-sectional survey study used a mixed methods triangulation design to validate and expand on quantitative findings using qualitative data. RESULTS: Quantitative and qualitative analyses revealed 13 pandemic stressor domains, with academics and lifestyle adjustment among the most stressful in both samples, and more stressful in the chronic pandemic sample. Non-freshmen, female, and first-generation college students were at greater risk for pandemic stress. CONCLUSIONS: As college students continue to experience stressors related to COVID-19 and encounter future crises, colleges and universities must adapt to meet their unique needs specific to the context.

The intersection of genome, epigenome and social experience in autism spectrum disorder: Exploring modifiable pathways for intervention.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades. Current research suggests that both genetic and environmental risk factors are involved in the etiology of ASD. The goal of this paper is to examine how one specific environmental factor, early social experience, may be correlated with DNA methylation (DNAm) changes in genes associated with ASD. We present an innovative model which proposes that polygenic risk and changes in DNAm due to social experience may both contribute to the symptoms of ASD. Previous research on genetic and environmental factors implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which may be epigenetically altered by early social experience, and which plays a crucial role in social and cognitive development. Identifying an environmental risk factor for ASD (e.g., social experience) that could be modified via early intervention and which results in epigenetic (DNAm) changes, could transform our understanding of this condition, facilitate earlier identification of ASD, and guide early intervention efforts.

Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy.

Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin-matrix interactions. However, it is increasingly recognized that resident cell junction proteins can be found in varying locations and with previously unrecognized functions. Our study here presents the nanoarchitecture and nanocolocalization of cell junction proteins in culture and tissue by stochastic optical reconstruction microscopy (STORM). The Z-axial view of noncancerous MDCK-II and PZ-HPV-7 cell-cell junctions resolved ß-catenin and p120ctn localizations to TJs and AJs, with p120ctn apical to ß-catenin and colocalizing with TJ protein claudin-7. More basally, p120ctn and ß-catenin become colocalized. This topography was lost in isogenic Ras-transformed MDCK cells and cancerous PC3 cells, where p120ctn becomes basally localized in relation to ß-catenin. Claudin-7 gene conditional knockout (cKO) in mice also have altered polarity of p120ctn relative to ß-catenin, like that seen in normal-to-cancer cell phenotypic transformation. Additionally, claudin-7 cKO resulted in redistribution and relocalization of other cell junction proteins, including claudin-1, zonula occludens-1, integrin α2, epithelial cell adhesion molecule, and focal adhesion kinase (FAK); specifically, integrin α2 and FAK were observed at the apical-lateral compartment. Our data show that STORM reveals regional cellular junction nanoarchitecture previously uncharacterized, providing new insight into potential trans-compartmental modulation of protein functions.

Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases.

Classical Rho GTPases, including RhoA, Rac1, and Cdc42, are members of the Ras small GTPase superfamily and play essential roles in a variety of cellular functions. Rho GTPase signaling can be turned on and off by specific GEFs and GAPs, respectively. These features empower Rho GTPases and their upstream and downstream modulators as targets for scientific research and therapeutic intervention. Specifically, significant therapeutic potential exists for targeting Rho GTPases in neurodegenerative diseases due to their widespread cellular activity and alterations in neural tissues. This study will explore the roles of Rho GTPases in neurodegenerative diseases with focus on the applications of pharmacological modulators in recent discoveries. There have been exciting developments of small molecules, nonsteroidal anti-inflammatory drugs (NSAIDs), and natural products and toxins for each classical Rho GTPase category. A brief overview of each category followed by examples in their applications will be provided. The literature on their roles in various diseases [e.g., Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), and Multiple sclerosis (MS)] highlights the unique and broad implications targeting Rho GTPases for potential therapeutic intervention. Clearly, there is increasing knowledge of therapeutic promise from the discovery of pharmacological modulators of Rho GTPases for managing and treating these conditions. The progress is also accompanied by the recognition of complex Rho GTPase modulation where targeting its signaling can improve some aspects of pathogenesis while exacerbating others in the same disease model. Future directions should emphasize the importance of elucidating how different Rho GTPases work in concert and how they produce such widespread yet different cellular responses during neurodegenerative disease progression.