Cellular differentiation is a fundamental strategy used by cells to generate specialized functions at specific stages of development. The bacterium employs a specialized dimorphic life cycle consisting of two differentiated cell types. How environmental cues, including mechanical inputs such as contact with a surface, regulate this cell cycle remain unclear. Here, we find that surface sensing by the physical perturbation of retracting extracellular pilus filaments accelerates cell-cycle progression and cellular differentiation. We show that physical obstruction of dynamic pilus activity by chemical perturbation or by a mutation in the outer-membrane pilus secretin CpaC stimulates early initiation of chromosome replication. In addition, we find that surface contact stimulates cell-cycle progression by demonstrating that surface-stimulated cells initiate early chromosome replication to the same extent as planktonic cells with obstructed pilus activity. Finally, we show that obstruction of pilus retraction stimulates the synthesis of the cell-cycle regulator cyclic diguanylate monophosphate (c-di-GMP) through changes in the activity and localization of two key regulatory histidine kinases that control cell fate and differentiation. Together, these results demonstrate that surface contact and sensing by alterations in pilus activity stimulate to bypass its developmentally programmed temporal delay in cell differentiation to more quickly adapt to a surface-associated lifestyle.
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http://dx.doi.org/10.1073/pnas.1920291117 | DOI Listing |
Mol Biol Cell
January 2025
Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA.
Asymmetric cell division (ACD) allows daughter cells of a polarized mother to acquire different developmental fates. In , the Wnt/β-catenin Asymmetry (WβA) pathway regulates many embryonic and larval ACDs; here, a Wnt gradient induces an asymmetric distribution of Wnt signaling components within the dividing mother cell. One terminal nuclear effector of the WβA pathway is the transcriptional activator SYS-1/β-catenin.
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January 2025
School of Pharmacy, Queen's University Belfast, Belfast BT9 7AF, UK.
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View Article and Find Full Text PDFClin Rheumatol
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Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Previous research has demonstrated ɑ7nAch receptor (ɑ7nAchR) agonists to provide benefit for rheumatoid arthritis (RA) patients. However, the immunological mechanism of action for these ɑ7nAchR agonists has not been elucidated. Herein, the effect of GTS-21, a selective ɑ7nAchR agonist, on the differentiation of Th17 and Th2 cells was assessed.
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) can be differentiated from invasive encapsulated follicular variant of papillary thyroid carcinoma (eFV-PTC) by the presence of a tumor capsule or blood vessel invasion in histological examination. The objective of this study was to investigate whether it is possible to distinguish between NIFTP and invasive eFV-PTC before surgery. Patients diagnosed with NIFTP and invasive eFV-PTC from 2017 to 2023 were analyzed for biochemical, ultrasonographic, and cytological features.
View Article and Find Full Text PDFDiscov Oncol
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Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, No. 58, Yuelu District, Changsha, 410006, Hunan, China.
Objective: Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD.
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