Publications by authors named "N Wolfson"
Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies. However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys.
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- A systematic literature review was conducted to investigate current practices for triaging and treating mangled extremities in resource-scarce environments (RSEs).
- The review involved a structured search and evaluation by multiple researchers, resulting in 58 articles being analyzed for their level and quality of evidence.
- The findings indicated a significant lack of strong evidence in existing studies, prompting a recommendation for further consensus-driven processes to update treatment guidelines specifically for RSEs.
Article Synopsis
- Histone deacetylases (HDACs) remove acetyl groups from proteins, but their specificity has mainly been studied using peptide substrates, raising questions about how well these reflect their behavior with full-length proteins.
- Research comparing HDAC8's action on peptides, full-length proteins, and protein-nucleic acid complexes reveals that it works much more efficiently on full-length histones than on peptides, suggesting additional interactions boost its activity.
- However, as the size of protein complexes increases, the efficiency decreases, indicating that HDAC8 substrate selectivity relies on a blend of short- and long-range interactions with the substrates.
HDAC8 is a member of the family of histone deacetylases (HDACs) that catalyze the deacetylation of acetyl lysine residues within histone and non-histone proteins. The recent identification of novel non-histone HDAC8 substrates such as SMC3, ERRα, and ARID1A indicates a complex functionality of this enzyme in cellular homeostasis. To discover additional HDAC8 substrates, we developed a comprehensive, structure-based approach based on Rosetta FlexPepBind, a protocol that evaluates peptide-binding ability to a receptor from structural models of this interaction.
View Article and Find Full Text PDFDespite being extensively characterized structurally and biochemically, the functional role of histone deacetylase 8 (HDAC8) has remained largely obscure due in part to a lack of known cellular substrates. Herein, we describe an unbiased approach using chemical tools in conjunction with sophisticated proteomics methods to identify novel non-histone nuclear substrates of HDAC8, including the tumor suppressor ARID1A. These newly discovered substrates of HDAC8 are involved in diverse biological processes including mitosis, transcription, chromatin remodeling, and RNA splicing and may help guide therapeutic strategies that target the function of HDAC8.
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