Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses.

The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation.

INFECTIONS IN AN EASTERN RATSNAKE () AND A TIMBER RATTLESNAKE ().

This report describes infections in colubrid and viperid snakes. A captive eastern ratsnake () was presented for a large intraoral mass associated with the mandible. The mass was debulked and histologic examination revealed severe, granulomatous stomatitis with intralesional fungi exhibiting morphologic features consistent with .

CCK Receptor Inhibition Reduces Pancreatic Tumor Fibrosis and Promotes Nanoparticle Delivery.

The poor prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is due in part to the highly fibrotic nature of the tumors that impedes delivery of therapeutics, including nanoparticles (NPs). Our prior studies demonstrated that proglumide, a cholecystokinin receptor (CCKR) antagonist, reduced fibrosis pervading PanIN lesions in mice. Here, we further detail how the reduced fibrosis elicited by proglumide achieves the normalization of the desmoplastic tumor microenvironment (TME) and improves nanoparticle uptake.

Nothing about us without us: Advocacy and engagement in genetic medicine.

The development of new genetic medicines to treat sickle cell disease highlights the need for greater collaboration between researchers and people with lived experiences. Drawing on the adage "Nothing about us, without us," we call for increased investments in community advocacy and engagement.