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Deep mutational scanning of the Trypanosoma brucei developmental regulator RBP6 reveals an essential disordered region influenced by positive residues.
Nat Commun
January 2025
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, 06536, USA.
To regain infectivity, Trypanosoma brucei, the pathogen causing Human and Animal African trypanosomiasis, undergoes a complex developmental program within the tsetse fly known as metacyclogenesis. RNA-binding protein 6 (RBP6) is a potent orchestrator of this process, however, an understanding of its functionally important domains and their mutational constraints is lacking. Here, we perform deep mutational scanning of the entire RBP6 primary structure.
View Article and Find Full Text PDFSphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.
J Cell Biol
April 2025
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.
View Article and Find Full Text PDFTGF-beta plays dual roles in immunity and pathogenesis in leishmaniasis.
Cytokine
January 2025
Department of Molecular Biology and Bioinformatics, Tripura University, Agartala, India. Electronic address:
Transforming growth factor-beta (TGF-β), displaying a dual role in immunosuppression and pathogenesis, has emerged as a key regulator of anti-leishmanial immune responses. In Leishmania infections, TGF-β drives immune deviation by enhancing regulatory T-cell (T-reg) differentiation and inhibiting macrophage activation, suppressing critical antiparasitic responses. This cytokine simultaneously promotes fibroblast proliferation, extracellular matrix production, and fibrosis in infected tissues, which aids in wound healing but impedes immune cell infiltration, particularly in visceral leishmaniasis, where splenic disorganization and compromised immune access are notable.
View Article and Find Full Text PDFAspartate Metabolism-Driven Gut Microbiota Dynamics and RIP-Dependent Mitochondrial Function Counteract Oxidative Stress.
Adv Sci (Weinh)
January 2025
Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan international joint laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Aspartate (Asp) metabolism-mediated antioxidant functions have important implications for neonatal growth and intestinal health; however, the antioxidant mechanisms through which Asp regulates the gut microbiota and influences RIP activation remain elusive. This study reports that chronic oxidative stress disrupts gut microbiota and metabolite balance and that such imbalance is intricately tied to the perturbation of Asp metabolism. Under normal conditions, in vivo and in vitro studies reveal that exogenous Asp improves intestinal health by regulating epithelial cell proliferation, nutrient uptake, and apoptosis.
View Article and Find Full Text PDFThe asymmetry engine: how plants harness asymmetries to shape their bodies.
New Phytol
January 2025
Department of Forest Genetics and Plant Physiology, Umeå Plant Science Centre (UPSC), Swedish University of Agricultural Sciences, 901 83, Umeå, Sweden.
Plant development depends on growth asymmetry to establish body plans and adapt to environmental stimuli. We explore how plants initiate, propagate, and regulate organ-wide growth asymmetries. External cues, such as light and gravity, and internal signals, including stochastic cellular growth variability, drive these asymmetries.
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