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A yeast-assembled, plasmid-launched reverse genetics system for the murine coronavirus MHV-A59.
J Gen Virol
January 2025
Biochemistry Program, The University of the South, Sewanee, TN, USA.
The murine hepatitis virus (MHV) is an important model system for studying coronavirus (CoV) molecular and cell biology. Despite this, few reagents for MHV are available through repositories such as ATCC or Addgene, potentially limiting the widespread adoption of MHV as a tractable model system. To overcome some challenges inherent in the existing MHV reverse genetics systems, we developed a plasmid-launched transformation-associated recombination (TAR) cloning-based system to assemble the MHV (strain A59; MHV-A59) genome.
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Alzheimers Dement
December 2024
University of Colorado School of Medicine, Aurora, CO, USA.
Background: Varicella zoster virus (VZV) reactivation, manifesting as herpes zoster, increases dementia risk. Herein, we review the literature supporting the biological plausibility of VZV contributing to AD pathologies and examine the unique ability of VZV to induce amylin that has been found in blood vessels and parenchyma of AD patients.
Method: We conducted a literature review on VZV and dementia to elucidate a potential model for how VZV reactivation intersects with AD.
Developing Topics.
Alzheimers Dement
December 2024
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Background: Early-onset Alzheimer's disease (EOAD) is a complex disease that occurs at an early age at onset (AAO) before 65 years, constituting 5-6% of all AD cases and remains poorly understood. Patient-derived induced pluripotent stem cells (iPSCs) have been used to model different forms of EOAD that display heterogeneous disease mechanisms.
Method: We examined iPSC-derived neurons from both familial EOAD harboring mutations in PSEN1 , PSEN2, and APP and non-familial EOAD patients at an early AAO.
Drug Development.
Alzheimers Dement
December 2024
University of California San Diego, La Jolla, CA, USA.
Background: Our lab has developed a CRISPR-based, gene-editing strategy that targets the extreme C-terminus (C-term) of APP (amyloid precursor protein) - a gene with a central and indisputable role in AD. We have reported previously that APP C-terminus CRISPRs effectively attenuate APP β-cleavage and Alzheimer's pathology in vivo. Here, we present new data demonstrating the feasibility and efficacy of a clinically-viable, "all-in-one" therapeutic vector that has all the components needed for APP C-terminus editing (Cas enzyme / gRNAs / regulatory elements) packaged into a single AAV.
View Article and Find Full Text PDFS6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.
Int J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
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