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http://dx.doi.org/10.1242/dev.201354 | DOI Listing |
Hematopoietic aging is characterized by chronic inflammation associated with myeloid bias, HSC accumulation, and functional HSC impairment. Yet it remains unclear how inflammation promotes these aging phenotypes. NFkappaB both responds to and directs inflammation, and we present an experimental model of elevated NFkappaB activity (IkappaBminus) to dissect its role in hematopoietic aging phenotypes.
View Article and Find Full Text PDFMouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood.
View Article and Find Full Text PDFUnlabelled: Compartmentalization of the nucleus into heterochromatin and euchromatin is highly conserved across eukaryotes. Constitutive heterochromatin (C-Het) constitutes a liquid-like condensate that packages the repetitive regions of the genome through the enrichment of histone modification H3K9me3 and recruitment of its cognate reader protein Heterochromatin Protein-1 (HP1a). The ability for well-ordered nucleosome arrays and HP1a to independently form biomolecular condensates suggests that the emergent material properties of C-Het compartments may contribute to its functions such as force-buffering, dosage-dependent gene silencing, and selective permeability.
View Article and Find Full Text PDFMany inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with innate training and can have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events.
View Article and Find Full Text PDFbioRxiv
January 2025
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90089, United States.
α-Synuclein (αSyn), an intrinsically disordered protein implicated in Parkinson's disease, is potentially thought to initiate aggregation through binding to cellular membranes. Previous studies have suggested that anionic membrane charge is necessary for this binding. However, these studies largely focus on unmodified αSyn, while nearly all αSyn in the body is N-terminally acetylated (NTA).
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