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Renewing tissues have the remarkable ability to continually produce both proliferative progenitor and specialized differentiated cell types. How are complex milieus of microenvironmental signals interpreted to coordinate tissue-cell-type composition? Here, we investigate the responses of intestinal epithelium to individual and paired perturbations across eight epithelial signaling pathways. Using a high-throughput approach that combines enteroid monolayers and quantitative imaging, we identified conditions that enrich for specific cell types as well as interactions between pathways. Importantly, we found that modulation of transit-amplifying cell proliferation changes the ratio of differentiated secretory to absorptive cell types. These observations highlight an underappreciated role for transit-amplifying cells in the tuning of differentiated cell-type composition.
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http://dx.doi.org/10.1016/j.devcel.2020.12.020 | DOI Listing |
Sud Med Ekspert
January 2025
Bureau of Forensic Medical Expertise, Saint-Petersburg, Russia.
Unlabelled: Forming wound canal is one of the main signs of gunshot wound. Its features are related to the following differential diagnostic signs: presence of gunshot wound, its intravitality, prescription, direction of projectile (bullet) movement, power of used weapon, etc.
Objective: To study the mechanisms of wound canal formation in gunshot injury, the pattern of damage to the biological tissues of its walls (mainly, blood vessels), the features of hemorrhages forming around it.
Elife
September 2025
Human Biology and Primate Evolution, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Evidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, with some TEs acting as deleterious elements while others are repurposed for beneficial roles in evolution. In mammals, some KRAB-ZNF proteins can serve as a key defense mechanism to repress TEs, offering genomic protection. Notably, the family of KRAB-ZNF genes evolves rapidly and exhibits diverse expression patterns in primate brains, where some TEs, including autonomous LINE-1 and non-autonomous Alu and SVA elements, remain mobile.
View Article and Find Full Text PDFNano Lett
September 2025
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.
View Article and Find Full Text PDFDev Growth Differ
September 2025
Department of Biological Sciences, College of Arts, Sciences, and Education, Florida International University, Miami, Florida, USA.
Superoxide dismutases (SODs) are key regulators of reactive oxygen species (ROS) and redox balance. Although intracellular SODs have been extensively studied, growing attention has been directed toward understanding the roles of extracellular SODs in both Dictyostelium and mammalian systems. In Dictyostelium discoideum, SodC is a glycosylphosphatidylinositol (GPI)-anchored enzyme that modulates extracellular superoxide to regulate Ras, PI3K signaling, and cytoskeletal remodeling during directional cell migration.
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