👤 Hemant Gujar

The human brain displays structural and functional disparities between its hemispheres, with such asymmetry extending to the frontal aslant tract. This plays a role in a variety of cognitive functions, including speech production, language processing, and executive functions. However, the factors influencing the laterality of the frontal aslant tract remain incompletely understood. Handedness is hypothesized to impact frontal aslant tract laterality, given its involvement in both language and motor control. In this study, we aimed to investigate the relationship between handedness and frontal aslant tract lateralization, providing insight into this aspect of brain organization. The Automated Tractography Pipeline was used to generate the frontal aslant tract for both right and left hemispheres in a cohort of 720 subjects sourced from the publicly available Human Connectome Project in Aging database. Subsequently, macrostructural and microstructural parameters of the right and left frontal aslant tract were extracted for each individual in the study population. The Edinburgh Handedness Inventory scores were used for the classification of handedness, and a comparative analysis across various handedness groups was performed. An age-related decline in both macrostructural parameters and microstructural integrity was noted within the studied population. The frontal aslant tract demonstrated a greater volume and larger diameter in male subjects compared with female participants. Additionally, a left-side laterality of the frontal aslant tract was observed within the general population. In the right-handed group, the volume ( The laterality of the frontal aslant tract appears to differ with handedness. This finding highlights the complex interaction between brain lateralization and handedness, emphasizing the importance of considering handedness as a factor in evaluating brain structure and function. Show less

In addition to mutations, epigenetic alterations are important contributors to malignant transformation and tumor progression. The aim of this work was to identify epigenetic events in which promoter or gene body DNA methylation induces gene expression changes that drive melanocyte malignant transformation and metastasis. We previously developed a linear mouse model of melanoma progression consisting of spontaneously immortalized melanocytes, premalignant melanocytes, a nonmetastatic tumorigenic, and a metastatic cell line. Here, through the integrative analysis of methylome and transcriptome data, we identified the relationship between promoter and/or gene body DNA methylation alterations and gene expression in early, intermediate, and late stages of melanoma progression. We identified adenylate cyclase type 3 (Adcy3) and inositol polyphosphate 4-phosphatase type II (Inpp4b), which affect tumor growth and metastatic potential, respectively. Importantly, the gene expression and DNA methylation profiles found in this murine model of melanoma progression were correlated with available clinical data from large population-based primary melanoma cohorts, revealing potential prognostic markers. Show less

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance. Show less