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SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.
Sci Rep
December 2024
Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ, USA.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined by a progressive decline in lung function due to scarring and accumulation of extracellular matrix (ECM) proteins. The SOCS (Suppressor Of Cytokine Signaling) domain is a 40 amino acid conserved domain known to form a functional ubiquitin ligase complex targeting the Von Hippel Lindau (VHL) protein for proteasomal degradation. Here we show that the SOCS conserved domain operates as a molecular tool, to disrupt collagen and fibronectin fibrils in the ECM associated with fibrotic lung myofibroblasts.
View Article and Find Full Text PDFNaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.
Nat Commun
December 2024
Department of Genetics, Yale University, Yale School of Medicine, New Haven, 06510, CT, USA.
The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).
View Article and Find Full Text PDFLocalized molecular chaperone synthesis maintains neuronal dendrite proteostasis.
Nat Commun
December 2024
Department of Biochemistry, McGill University, Montreal, QC, Canada.
Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.
View Article and Find Full Text PDFNeoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.
Nat Commun
December 2024
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).
View Article and Find Full Text PDFPediatric Acute Otitis Media Clinical Trials: An Analysis of Diversity.
Otolaryngol Head Neck Surg
December 2024
Department of Otolaryngology-Head and Neck Surgery, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Objective: This study aims to assess the diversity and equity of pediatric acute otitis media (AOM) trials using ClinicalTrials.gov, focusing on participant demographics and representation to identify gaps in inclusivity and inform strategies for promoting diversity in future pediatric AOM studies.
Study Design: Retrospective analysis.
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