Publications by authors named "P H ADAMS"
Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH). While increasing HCC risk, MASH triggers p53-dependent hepatocyte senescence, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear.
View Article and Find Full Text PDFSenescent cells drive tissue dysfunction through the senescence-associated secretory phenotype (SASP). We uncovered a central role for mitochondria in the epigenetic regulation of the SASP, where mitochondrial-derived metabolites, specifically citrate and acetyl-CoA, fuel histone acetylation at SASP gene loci, promoting their expression. We identified the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY) as critical for this process.
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- Flagella are crucial for the movement of pathogens like the Lyme spirochete Borrelia burgdorferi, but their production is costly and triggers immune responses, leading to complex regulatory systems controlling their gene expression.
- The study identifies the gene bb0268 (flgV) in B. burgdorferi as a structural component of the flagella, rather than the previously thought RNA-binding protein, which plays a significant role in flagellar assembly.
- FlgV is essential for producing functional flagella and affects the bacteria's motility and ability to infect hosts, highlighting its importance in the pathogen's life cycle, especially during infection phases.
Article Synopsis
- * Aged individuals showed an increase in macrophages with a tolerogenic phenotype and dysfunctional CD8-positive T cells, while profibrotic macrophages were reduced.
- * Inhibiting TREM1 decreased melanoma growth in younger mice, whereas inhibiting TREM2 helped prevent lung metastasis in older mice, suggesting new treatment targets for age-related melanoma immunotherapy.