Scholarly Works, School of Neuroscience
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Browsing Scholarly Works, School of Neuroscience by Subject "31 Biological Sciences"
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- Pediatric diffuse hemispheric glioma H3 G34-mutant with gains of the BRAF locus: An illustrative caseMarlow, Christine; Cuoco, Joshua A.; Hoggarth, Austin R.; Stump, Michael S.; Apfel, Lisa S.; Rogers, Cara M. (SAGE, 2023-03)Diffuse hemispheric glioma, H3 G34-mutant, is a recently recognized distinct high-grade glioma with a dismal prognosis. In addition to the H3 G34 missense mutation, numerous genetic events have been identified in these malignant tumors, including ATRX, TP53, and, rarely, BRAF genes. There are only a few reports to date that have identified BRAF mutations in diffuse hemispheric glioma, H3 G34-mutant. Moreover, to our knowledge, gains of the BRAF locus have yet to be described. Here, we present a case of an 11-year-old male with a diffuse hemispheric glioma, H3 G34-mutant, found to have novel gains of the BRAF locus. Furthermore, we emphasize the current genetic landscape of diffuse hemispheric glioma, H3 G34-mutant, and implications of an aberrant BRAF signaling pathway.
- Remdesivir increases mtDNA copy number causing mild alterations to oxidative phosphorylationDeFoor, Nicole; Paul, Swagatika; Li, Shuang; Basso, Erwin K. Gudenschwager; Stevenson, Valentina; Browning, Jack L.; Prater, Anna K.; Brindley, Samantha; Tao, Ge; Pickrell, Alicia M. (Springer, 2023-12-01)SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to mitochondrial DNA (mtDNA). These past findings on the mitochondrial toxicity of ribonucleoside analogues motivated us to investigate what effects RDV may have on mitochondrial function. Using in vitro and in vivo rodent models treated with RDV, we observed increases in mtDNA copy number in Mv1Lu cells (35.26% increase ± 11.33%) and liver (100.27% increase ± 32.73%) upon treatment. However, these increases only resulted in mild changes to mitochondrial function. Surprisingly, skeletal muscle and heart were extremely resistant to RDV treatment, tissues that have preferentially been affected by other nucleoside analogues. Although our data suggest that RDV does not greatly impact mitochondrial function, these data are insightful for the treatment of RDV for individuals with mitochondrial disease.