Panday, P. | bioRxiv Science

bioRxiv2024

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Although targeted radiotherapy (RT) is integral to the increasing survival of cancer patients, it has significant side-effects, the cellular and molecular mechanisms of which are not fully understood. During RT epigenetic changes occur in neoplastic tissue, but few studies have assessed these in non-neoplastic tissue and results are highly variable. Using bulk DNA methylation and RNA sequencing as well as spatial transcriptomics (ST) in a unique cohort of patient tissue samples, we show distinct differences in DNA methylation patterns in irradiated brain tissue, whilst ST characterisation identifies specific micro-environmental niches present after irradiation and highlights neuropeptides that could be propagating neuroinflammation. We also show that in a cerebral organoid (CO) model of early changes in neurons after irradiation there are similar DNA methylation alterations and disruption of the DNA methylation machinery, suggesting that early but persistent epigenetic dysregulation plays a role in neurotoxicity. We provide a link between radiotherapy induced neuroinflammation and disruption of DNA methylation for the first time and suggest possible driving mechanisms for this chronic neuroinflammation.

neuroscience↗

bioRxiv2019

Climate change and deforestation boost post-fire grass invasion of Amazonian forests

Interactions among climate change, deforestation and fires are changing the stability of the Amazon forest, and may promote transitions to degraded grassy ecosystem states. However, our ability to predict the locations in the Amazon that are most vulnerable to these transitions is limited. In this study we used a dynamic carbon model to evaluate how drought, climate change and deforestation could affect the probability of post-fire grass invasion across the Amazon, and identify where grass-fire feedbacks may promote the persistence of species-poor degraded forests with savanna-like structure. Our results suggest that, under current climatic conditions, post-fire grass invasion could affect 11% of the Amazon, with the south-eastern Amazon at highest risk of invasion. We forecast that under business as usual climate change, by the end of the century areas with a high probability of post-fire grass invasion will increase to 20% of the Amazon. In 10% of the Amazon fire return interval will be shorter than the time required for canopy recovery, implying high risk of irreversible shifts to a fire-maintained degraded ecosystem state. Although resilience in canopy regeneration is evident in areas with low fire frequency, increased fire frequency could inhibit regeneration even in forests where grass is currently excluded, and push the Amazon forests towards a tipping point causing large areas of forest to transition to low tree cover state.

ecology↗