2,759 research outputs found
Gaia contributions to agroecology by James Lovelock (1919-2022)
In writing about the history of agroecology we too often ignore the valuable contributions of British scientist James Lovelock who recently died on his 103rd birthday. A prolific inventor and influential theorist, Lovelock is best known for the Gaia hypothesis first proposed during his innovative work in the 1960s with NASA. He suggested that ‘the biosphere has a regulatory effect on the Earth’s environment that acts to sustain life’ as written in Gaia: A New Look at Life on Earth (Lovelock 1979). Lovelock further proposed that humans have strongly impacted the planet’s capacity to maintain this vast, living, self-regulating system
Functional Analysis of Non-Genetic Resistance to Platinum in Epithelial Ovarian Cancer Reveals a Role for the MBD3-NuRD Complex in Resistance Development
Epithelial ovarian cancer (EOC) is the most lethal disease of the female reproductive tract, and although most patients respond to the initial treatment with platinum (cPt)-based compounds, relapse is very common. We investigated the role of epigenetic changes in cPt-sensitive and -resistant EOC cell lines and found distinct differences in their enhancer landscape. Clinical data revealed that two genes (JAK1 and FGF10), which gained large enhancer clusters in resistant EOC cell lines, could provide novel biomarkers for early patient stratification with statistical independence for JAK1. To modulate the enhancer remodeling process and prevent the acquisition of cPt resistance in EOC cells, we performed a chromatin-focused RNAi screen in the presence of cPt. We identified subunits of the Nucleosome Remodeling and Deacetylase (NuRD) complex as critical factors sensitizing the EOC cell line A2780 to platinum treatment. Suppression of the Methyl-CpG Binding Domain Protein 3 (MBD3) sensitized cells and prevented the establishment of resistance under prolonged cPt exposure through alterations of H3K27ac at enhancer regions, which are differentially regulated in cPt-resistant cells, leading to a less aggressive phenotype. Our work establishes JAK1 as an independent prognostic marker and the NuRD complex as a potential target for combinational therapy
- …