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The pseudouridylase Pus1 catalyzes pseudouridine (Ψ) formation at multiple uridine residues in tRNAs, and in some snRNAs and mRNAs. Although Pus1 is highly conserved, and mutations are associated with human disease, little is known about eukaryotic Pus1 biology. Here, we show that Schizosaccharomyces pombe pus1Δ mutants are temperature sensitive due to decay of tRNAIle(UAU), as tRNAIle(UAU) levels are reduced, and its overexpression suppresses the defect.
View Article and Find Full Text PDFCellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis.
Biol Open
January 2025
Faculty of Biology Medicine and Health, The University of Manchester, Manchester M13 9PT, UK.
In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear.
View Article and Find Full Text PDFMetabolic activities are selective modulators for individual segmentation clock processes.
Nat Commun
January 2025
European Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Numerous cellular and molecular processes during embryonic development prompt the fundamental question of how their tempos are coordinated and whether a common global modulator exists. While the segmentation clock tempo scales with the kinetics of gene expression and degradation processes of the core clock gene Hes7 across mammals, the coordination of these processes remains unclear. This study examines whether metabolic activities serve as a global modulator for the segmentation clock, finding them to be selective instead.
View Article and Find Full Text PDFSomatic PTEN and ARID1A loss and endometriosis disease burden: a longitudinal study.
Hum Reprod
December 2024
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Study Question: Is there an association between the somatic loss of PTEN (phosphatase and tensin homolog) and ARID1A (AT-rich interaction domain 1A) and endometriosis disease severity and worse clinical outcomes?
Summary Answer: Somatic PTEN loss in endometriosis epithelium was associated with greater disease burden and subsequent surgical complexity.
What Is Known Already: Somatic cancer-driver mutations including those involving the PTEN and ARID1A genes exist in endometriosis without cancer; however, their clinical impact remains unclear.
Study Design, Size, Duration: This prospective longitudinal study involved endometriosis tissue and clinical data from 126 participants who underwent surgery at a tertiary center for endometriosis (2013-2017), with a follow-up period of 5-9 years.
Physiological significance of antithrombin D-helix interaction with vascular GAGs.
Blood Adv
December 2024
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States.
Antithrombin (AT) is an anticoagulant serpin involved in the regulation of proteolytic activities of coagulation proteases. AT also possesses a direct anti-inflammatory function. The anticoagulant function of AT is mediated through its reactive-center loop (RCL)-dependent inhibition of coagulation proteases, but anti-inflammatory function of AT is mediated via its D-helix-dependent interaction with vascular glycosaminoglycans (GAGs).
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