RESUMO
Macroautophagy is thought to have a critical role in shaping and refining cellular proteostasis in eukaryotic cells recovering from DNA damage. Here, we report a mechanism by which autophagy is suppressed in cells exposed to bacterial toxin-, chemical-, or radiation-mediated sources of genotoxicity. Autophagy suppression is directly linked to cellular responses to DNA damage, and specifically the stabilization of the tumor suppressor p53, which is both required and sufficient for regulating the ubiquitination and proteasome-dependent reduction in cellular pools of microtubule-associated protein 1 light chain 3 (LC3A/B), a key precursor of autophagosome biogenesis and maturation, in both epithelial cells and an ex vivo organoid model. Our data indicate that suppression of autophagy, through a newly identified p53-proteasome-LC3 axis, is a conserved cellular response to multiple sources of genotoxicity. Such a mechanism could potentially be important for realigning proteostasis in cells undergoing DNA damage repair.
RESUMO
This article discusses the laser-assisted turbinectomy (LATE) procedure and indications for its performance in dogs suffering from brachycephalic obstructive airway syndrome (BOAS). The article summarizes landmark works that reported, for the first time, endoscopic-assisted identification and treatment of structures within the brachycephalic nose that contribute to intranasal obstruction and resistance to breathing, specifically hypertrophic and aberrant nasal turbinates. Brachycephaly is discussed in the context of how these aberrations form and how definitive treatments such as LATE and adjunctive treatments such as ala vestibuloplasty, folded flap palatoplasty, and others may ameliorate the negative effects and improve patient outcomes associated with aberrant intranasal conchal configurations.