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.

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The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades with current research unable to fully account for this dramatic increase in prevalence. One explanation proposes that both intrinsic (e.g., genetic) and extrinsic (e.g., environmental) risk factors may be involved in the etiology of ASD. The goal of this review paper is to explore modifiable pathways for intervention in children at risk for ASD, specifically examining how early social experience may be correlated with epigenetic change in genes associated with autism. We present an innovative model which proposes that polygenic risk and social experience (via epigenetic mechanisms) may both contribute to the observed ASD phenotype. Previous research on genetic, environmental, and epigenetic mechanisms implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which is epigenetically altered by early social experience, plays a crucial role in mammalian social and cognitive development, and is associated with both genetic and epigenetic risk for ASD. Identifying intrinsic (e.g., genetic) and extrinsic (e.g., social experience) risk markers for ASD, a combination of which has not previously been examined, would transform our understanding of this condition, facilitate earlier identification of ASD risk, and guide early intervention efforts. This may have a far-reaching impact on individuals with ASD, their families, and society.

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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 β‐catenin and p120ctn localizations to TJs and AJs, with p120ctn apical to β‐catenin and colocalizing with TJ protein claudin‐7. More basally, p120ctn and β‐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 β‐catenin. Claudin‐7 gene conditional knockout (cKO) in mice also have altered polarity of p120ctn relative to β‐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.

Background: Koru is a 4-week group mindfulness-based intervention that previously demonstrated psychological benefits in university students through its offering via a counseling center (Greeson, Juberg, Mayatan, James, & Rogers, 2014). Aim: This study examined the feasibility of Koru offered universally to students via collaborative outreach (i.e., student interest, attendance, adverse events, participant acceptability, and participant willingness to complete assessments). Method: Across five semesters, Koru was advertised via flyers, emails to student organizations and faculty and staff, and counseling center referrals at a southeastern public university with 29,000-students. Interested students were randomly assigned to Koru or a waitlist. In-person Koru groups took place in classrooms on campus. Assessments included practice logs, program evaluations, and pre- and post-intervention surveys measuring mindfulness and psychological symptoms. Results: Interest was sufficient to offer 2-3 groups per semester (171 students). Of those assigned to Koru, 44.4% completed 3-4 sessions and 34.9% did not attend any sessions. The adverse event rate was 2.9%. Evaluations were positive and all participants attending the last session completed them. The response rate was 29.0% for log completion and 17.9% for survey completion. Conclusion: Results support student interest in, and acceptability of Koru offered to all students on campus outside of a counseling center. Data collection was challenging.

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 their characteristic resident proteins can be found in each other's territories and demonstrate previously unrecognized functions. This study presents the nanoarchitecture and nano‐colocalization of cell junction proteins in culture and in intestinal tissue by Stochastic Optical Reconstruction Microscopy (STORM). STORM allows for resolution of approximately 20 nm in the xy plane and 50 nm in the z plane. The Z‐axial view of non‐cancerous MDCK‐II cell AJ proteins, β‐catenin and p120ctn, showed greatest expression density towards the apical milieu of AJ. This is accompanied by the distinctive displacement of p120ctn being apical to β‐catenin. Towards the basal direction, p120ctn and β‐catenin become increasingly colocalized. Interestingly, this topography is lost in metastatic prostate cancer PC3 cells, in that p120ctn localization becomes basal to β‐catenin. The deletion of TJ protein claudin‐7 is sufficient in altering the polarity of p120ctn to basal β‐catenin localization, like that seen in PC3 cells compared to MDCK‐II. Loss of claudin‐7 also significantly altered localization and distribution of many cell junction proteins. Therefore, STORM revealed the regional nanoarchitecture of cellular junctions that were previously unavailable, providing new insights in their potential trans‐compartmental modulation of protein functions.