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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Texas Medical Branch, Galveston, TX, USA.
Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder leading to dementia. The existence of individuals who remain cognitively intact despite presenting histopathological signs of AD, here referred to as "Non-demented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. These individuals are distinguished by the presence of highly phagocytic microglia capable of clearing damaged synapses near plaques, mitigating further damage to axons and dendrites.
View Article and Find Full Text PDFPhase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.
Neurooncol Adv
November 2024
Huntsman Cancer Institute, Salt Lake City, UT, USA.
Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.
View Article and Find Full Text PDFDevelopment and characterization of fluorescent cholesteryl probes with enhanced solvatochromic and pH-sensitive properties for live-cell imaging.
Sci Rep
December 2024
Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science, Florida Atlantic University, 777 Glades Rd, Boca Raton, FL, 33431, USA.
We present novel fluorescent cholesteryl probes (CNDs) with a modular design based on the solvatochromic 1,8-phthalimide scaffold. We have explored how different modules-linkers and head groups-affect the ability of these probes to integrate into lipid membranes and how they distribute intracellularly in mouse astrocytes and fibroblasts targeting lysosomes and lipid droplets. Each compound was assessed for its solvatochromic behavior in organic solvents and model membranes.
View Article and Find Full Text PDFEfficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.
Front Immunol
December 2024
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
The functional specialization of CD4 T lymphocytes into various subtypes, including T1 and T cells, is crucial for effective immune responses. T cells facilitate B cell differentiation within germinal centers, while T1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling.
View Article and Find Full Text PDFExperimental and computational investigations of RNA duplexes containing N7-regioisomers of adenosine and LNA-adenosine.
Nucleic Acids Res
December 2024
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Although glycosidic bonds in purines typically involve the N9 position, the chemical synthesis of adenosine produces N7-ribofuranosyladenine (7A) as a kinetically favorable ribosylation product. Similarly, in the synthesis of LNA-adenosine (AL), a minor product, N7-LNA-adenosine (7AL), is observed. While extensive research has focused on investigating the properties of N9-regioisomers of adenosine, 7A has been largely overlooked and considered as a side-product.
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