The parasubthalamic nucleus refeeding ensemble delays feeding initiation and hastens water drinking.

The parasubthalamic nucleus (PSTN) is activated by refeeding after food deprivation and several PSTN subpopulations have been shown to suppress feeding. However, no study to date directly addressed the role of PSTN neurons activated upon food access in the control of ensuing food consumption. Here we identify consumption latency as a sensitive behavioral indicator of PSTN activity, and show that, in hungry mice, the ensemble of refeeding-activated PSTN neurons drastically increases the latency to initiate refeeding with both familiar and a novel, familiar food, but does not control the amount of food consumed.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

Introduction: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE.

Methods: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants.

Nuclear export inhibition jumbles epithelial-mesenchymal states and gives rise to migratory disorder in healthy epithelia.

Dynamic nucleocytoplasmic transport of E-M factors regulates cellular E-M states; yet, it remains unknown how simultaneously trapping these factors affects epithelia at the macroscale. To explore this question, we performed nuclear export inhibition (NEI) via leptomycin B and Selinexor treatment, which biases nuclear localization of CRM1-associated E-M factors. We examined changes in collective cellular phenotypes across a range of substrate stiffnesses.

Nucleoli in epithelial cell collectives respond to tumorigenic, spatial, and mechanical cues.

Cancer cells are known to have larger nucleoli, consistent with their higher transcriptional and translational demands. Meanwhile, on stiff extracellular matrix, normal epithelial cells can exhibit genomic and proteomic mechanoactivation toward tumorigenic transformations, such as epithelial-mesenchymal transition and enhanced migration. However, while nucleolar bodies regulate the protein synthesis required for mechanosensation, it remains unknown whether mechanical and spatial extracellular cues can in turn alter nucleoli.

Pericellular heparan sulfate proteoglycans: Role in regulating the biosynthetic response of nucleus pulposus cells to osmotic loading.

Background: Daily physiologic loading causes fluctuations in hydration of the intervertebral disc (IVD); thus, the embedded cells experience cyclic alterations to their osmotic environment. These osmotic fluctuations have been described as a mechanism linking mechanics and biology, and have previously been shown to promote biosynthesis in chondrocytes. However, this phenomenon has yet to be fully interrogated in the IVD.