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1.
Nat Immunol ; 24(10): 1698-1710, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37592014

RESUMO

In development, pioneer transcription factors access silent chromatin to reveal lineage-specific gene programs. The structured DNA-binding domains of pioneer factors have been well characterized, but whether and how intrinsically disordered regions affect chromatin and control cell fate is unclear. Here, we report that deletion of an intrinsically disordered region of the pioneer factor TCF-1 (termed L1) leads to an early developmental block in T cells. The few T cells that develop from progenitors expressing TCF-1 lacking L1 exhibit lineage infidelity distinct from the lineage diversion of TCF-1-deficient cells. Mechanistically, L1 is required for activation of T cell genes and repression of GATA2-driven genes, normally reserved to the mast cell and dendritic cell lineages. Underlying this lineage diversion, L1 mediates binding of TCF-1 to its earliest target genes, which are subject to repression as T cells develop. These data suggest that the intrinsically disordered N terminus of TCF-1 maintains T cell lineage fidelity.


Assuntos
Linfócitos T , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Linfócitos T/metabolismo , Fator 1 de Transcrição de Linfócitos T/genética , Cromatina/metabolismo
2.
Materials (Basel) ; 14(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34947276

RESUMO

Medical devices with antimicrobial properties are a potential long-term solution to the high rate of multi-drug-resistant healthcare-associated infections. Silver nanoparticles (AgNPs) are an established agent for effectively eliminating a wide range of microbial strains. AgNPs have been commonly incorporated into traditional plastic materials; however, recently, there has been increased interest in using AgNPs combined with 3D-printing technology for medical devices due to the accessibility and customizability of 3D-printed products. This study reports a novel method of utilizing acetone to partially dissolve 3D-printed polymer acrylonitrile butadiene styrene (ABS) plastic to attach a layer of AgNPs. The antimicrobial properties of this AgNP-coated surface were tested against several microbial strains prevalent in healthcare-associated infections. AgNP-coated ABS (AgNP-ABS) plastic demonstrated significant elimination of viable bacteria within 4 h for all tested bacterial species (Acinetobacter baumannii, non-pathogenic and pathogenic Escherichia coli, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus) and within 19 h for the tested fungus Candida albicans. The longevity of adhesion of AgNPs to the ABS plastic was assessed by checking antibacterial activity against A. baumannii after repeat use cycles. AgNP-ABS plastic showed decreased antibacterial efficacy with repeated use but maintained the ability to eliminate microbes within 3 h for up to eight use cycles. The AgNP-coated ABS plastic showed efficacy as an antimicrobial surface, and future studies will consider its applicability in the production of medical devices.

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