A Structural Mechanism for Noncanonical GPCR Signal Transduction in the Hedgehog Pathway.

The Hedgehog (Hh) signaling pathway is fundamental to embryogenesis, tissue homeostasis, and cancer. Hh signals are transduced via an unusual mechanism: upon agonist-induced phosphorylation, the noncanonical G protein-coupled receptor SMOOTHENED (SMO) binds the catalytic subunit of protein kinase A (PKA-C) and physically blocks its enzymatic activity. By combining computational structural approaches with biochemical and functional studies, we show that SMO mimics strategies prevalent in canonical GPCR and PKA signaling complexes, despite little sequence or secondary structural homology.

Yield of MR-directed US for MRI-detected breast findings: how often can we avoid MR biopsy?

Purpose: To evaluate the yield of MR-directed ultrasound for MRI detected breast findings.

Methods: This retrospective study included 857 consecutive patients who had a breast MRI between January 2017-December 2020 and received a BI-RADS 4 assessment. Only exams recommended for MR-directed ultrasound were included in the study, yielding 765 patients.

Reported Methods, Distributions, and Frequencies of Torture Globally: A Systematic Review and Meta-Analysis.

Importance: Despite its prohibition by the United Nations Convention against Torture and other international treaties, torture has been perpetrated against countless individuals worldwide, and health care practitioners globally are increasingly encountering refugee torture survivors in their clinical practices. The methods, geographic distribution, and frequency of torture globally are not well described, which limits health care practitioners' ability to adequately diagnose and treat the sequelae of torture.

Objective: To rank the commonness of torture methods and identify the regions of the world with which they are associated.

Camouflaging in Developmental Language Disorder: The Views of Speech and Language Pathologists and Parents.

The term describes behaviors that cover up neurodivergent difficulties. While researched in autism, camouflaging has received no systematic study in other conditions affecting communication, including developmental language disorder (DLD). This study explored camouflaging in DLD, drawing on the experience and expertise of speech and language pathologists and parents of children with DLD.

GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the vertebrate primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction.

Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using Synechococcus elongatus PCC 7942.

Photosynthetic conversion of CO2 to chemicals using cyanobacteria is an attractive approach for direct recycling of CO2 to useful products. 3-Hydroxypropionic acid (3 HP) is a valuable chemical for the synthesis of polymers and serves as a precursor to many other chemicals such as acrylic acid. 3 HP is naturally produced through glycerol metabolism.