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Regionally distinct GFAP promoter expression plays a role in off-target neuron expression following AAV5 transduction.
Sci Rep
December 2024
Institute of Medical Sciences, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Astrocyte to neuron reprogramming has been performed using viral delivery of neurogenic transcription factors in GFAP expressing cells. Recent reports of off-target expression in cortical neurons following adeno-associated virus (AAV) transduction to deliver the neurogenic factors have confounded our understanding of the efficacy of direct cellular reprogramming. To shed light on potential mechanisms that may underlie the neuronal off-target expression of GFAP promoter driven expression of neurogenic factors in neurons, two regionally distinct cortices were compared-the motor cortex (MC) and medial prefrontal cortex (mPFC)-and investigated: (1) the regional tropism and astrocyte transduction with an AAV5-GFAP vector, (2) the expression of Gfap in MC and mPFC neurons; and (3) material transfer between astrocytes and neurons.
View Article and Find Full Text PDFGATD3A-deficiency-induced mitochondrial dysfunction facilitates senescence of fibroblast-like synoviocytes and osteoarthritis progression.
Nat Commun
December 2024
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression. Here, we elucidate a positive correlation between fibroblast-like synoviocyte senescence and osteoarthritis progression and reveal that GATD3A deficiency induces fibroblast-like synoviocyte senescence.
View Article and Find Full Text PDFMagnetosensitivity of tightly bound radical pairs in cryptochrome is enabled by the quantum Zeno effect.
Nat Commun
December 2024
Living Systems Institute, University of Exeter, Stocker Road, Exeter, Devon, EX4 4QD, UK.
The radical pair mechanism accounts for the magnetic field sensitivity of a large class of chemical reactions and is hypothesised to underpin numerous magnetosensitive traits in biology, including the avian compass. Traditionally, magnetic field sensitivity in this mechanism is attributed to radical pairs with weakly interacting, well-separated electrons; closely bound pairs were considered unresponsive to weak fields due to arrested spin dynamics. In this study, we challenge this view by examining the FAD-superoxide radical pair within cryptochrome, a protein hypothesised to function as a biological magnetosensor.
View Article and Find Full Text PDFDistinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.
Mol Neurodegener
December 2024
German Center for Neurodegenerative Diseases (LMU), Klinikum, Germany.
Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.
View Article and Find Full Text PDFEnhanced visible-light-driven photocatalytic antibacterial activity by in-situ synthesized NH-MIL-101(Al)/AgI heterojunction and mechanism insight.
Environ Res
December 2024
Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China. Electronic address:
Photocatalytic antibacterial technology has the potential to prevent the formation of biofilms and microbial corrosion of metals by rapidly eliminating microorganisms in a short period. In this study, novel NH-MIL-101(Al)/AgI is in-situ synthesized at ambient temperature, revealing enhanced photocatalytic antibacterial activity and cyclic stability in seawater. A low dosage of 0.
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