Publications by authors named "R L Hite"
DNA G-quadruplexes (G4s) are non-B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork collisions with preformed G4s in the parental DNA using reconstituted yeast and human replisomes. We demonstrate that a single G4 in the leading strand template is sufficient to stall replisomes by arresting the CMG helicase.
View Article and Find Full Text PDFArchitecture and activation of single-pass transmembrane receptor guanylyl cyclase.
Nat Struct Mol Biol
November 2024
The heart, in addition to its primary role in blood circulation, functions as an endocrine organ by producing cardiac hormone natriuretic peptides. These hormones regulate blood pressure through the single-pass transmembrane receptor guanylyl cyclase A (GC-A), also known as natriuretic peptide receptor 1. The binding of the peptide hormones to the extracellular domain of the receptor activates the intracellular guanylyl cyclase domain of the receptor to produce the second messenger cyclic guanosine monophosphate.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates a specific genetic variant in the IP3 receptor that results in a significant disorder affecting multiple systems, characterized by immunodeficiency and disturbed calcium release in cells.
- The variant (c.7570C>T, p.Arg2524Cys) leads to cellular defects, particularly impacting T cells, and is shown to affect calcium regulation and mitochondrial function, evidenced in laboratory models.
- Patients exhibited a range of symptoms beyond immunodeficiency, such as ectodermal dysplasia and short stature, suggesting that this genetic mutation plays a unique and broader role in disease compared to previously documented cases.
TMEM175 is a lysosomal potassium and proton channel that is associated with the development of Parkinson's disease. Advances in understanding the physiological roles of TMEM175 have been hampered by the absence of selective inhibitors, and studies involving genetic perturbations have yielded conflicting results. Here, we report the discovery and characterization of the first reported TMEM175-selective inhibitors, 2-phenylpyridin-4-ylamine (2-PPA), and AP-6.
View Article and Find Full Text PDFImportance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates.
Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo.
Design, Setting, And Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up.