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Barot, S.

Publications and source records attributed to Barot, S..

4 recordsLinked to original sources

Mitochondrial Dysfunction and Senescence Accompany Glioblastoma Cell Death Triggered by a Putative Metabolic Inhibitor

Glioblastoma (GBM) is a fatal cancer with a dismal prognosis and a dire need for novel chemotherapeutics. Metabolic reprogramming is an established hallmark of cancer. In our previous study on GBM, we aimed at targeting the metabolic reprogramming of cancer by using stiripentol (STP), a putative lactate dehydrogenase (LDH) inhibitor and an FDA-approved anti-epileptic drug. However, the precise mechanism of STPs anti-cancer activity remains unclear. We aimed to elucidate the mechanism of action of STP in GBM to further develop STP as a therapeutic. We employed a multiomic approach followed by metabolic and cellular assays. STP treatment induced genetic and metabolic alterations in GBM cells. Inhibition of LDH by STP was moderate but not potent. The cellular changes were accompanied by an increase in reactive oxygen species, a decrease in mitochondrial membrane potential, and induction of senescence in GBM cells. Our research indicates that further research in senescence-inducing agents and novel LDH inhibitors can provide novel therapeutics for GBM.

pharmacology and toxicology↗

Spatial context allows the evolution the control of nitrification by plants

Some plant species inhibit or stimulate soil nitrification, the transformation of ammonium into nitrate by microorganisms. The control of nitrification may in turn alter ecosystem productivity and functioning. Given the potential positive impacts of nitrification control on plant fitness, we aim to determine the conditions under which nitrification control is likely to have been selected, and the consequences of that selection on ecosystem functioning. We investigate both the role of the abiotic context (nutrient availability and diffusion) and the role of other plant traits (mortality and dispersal). A first mean-field model shows that when nitrogen pools are shared among individuals within the plant population, the control of nitrification is counter-selected. A tragedy of the commons occurs because the costs of controlling nitrification (ie. of producing root exudates) only affect the controlling individuals while benefits are shared among all individuals. We then assume that the effects of the control of nitrification are spatially restricted to the rhizosphere, and we build a spatially explicit, individual-based model in which mutation of control of nitrification is possible. Plant capacity to control nitrification evolves when the plant environment is sufficiently private and generation time sufficiently long, leading to higher fitness benefits of the construction process. In such cases, plants evolve to inhibit nitrification when losses of nitrate are greater than losses of ammonium and evolve to stimulate nitrification when losses of ammonium are greater than losses of nitrate. Finally, biomass production tends to be maximal at the selected strategy when the diffusion of ammonium and nitrate is low. Our results help predict which strategies should be selected and likely to be found in different plants in different parts of the world.

ecology↗

Diffusion of constructed resources and specialism promotes facilitation in spatial systems

Sessile organisms contend with locally limiting nutrients and neighbours. Increases in nutrient concentration due to niche construction and diffusion of resources change the interaction sign between neighbours usually thought to compete for resources. We investigate conditions under which the positive effect of niche construction outweighs the negative effect of resource consumption. Following the design of facilitation experiments, we model two patches connected by resource flows, and ask whether the presence of a niche constructor in one patch eases the colonisation of the other. Niche constructors positively affect neighbouring organisms when their niches are sufficiently differentiated, and when the constructed resource diffuses more than the non-constructed resource. Our work proposes mechanisms for the emergence of facilitation, which is increasingly recognised as a key process structuring plant and microbial communities. We discuss the implications for the spatial structure of communities and their functioning, including in an agricultural context.

ecology↗

Impact of nutrient cycling on food web stability

AO_SCPLOWBSTRACTC_SCPLOWNutrient cycling is fundamental to ecosystem functioning. Despite recent major advances in the understanding of complex food web dynamics, food web models have so far generally ignored nutrient cycling. However, nutrient cycling is expected to strongly impact food web stability and functioning. To make up for this gap, we built an allometric and size structured food web model including nutrient cycling. By releasing mineral nutrients, recycling increases the availability of limiting resources for primary producers and links each trophic level to the bottom of food webs. We found that nutrient cycling can provide a significant part of the total nutrient supply of the food web, leading to a strong enrichment effect that promotes species persistence in nutrient poor ecosystems but leads to a paradox of enrichment at high nutrient inputs. The presence of recycling loops linking each trophic level to the basal resources weakly affects species biomass temporal variability in the food web. Recycling loops tend to slightly dampen the destabilising effect of nutrient enrichment on consumer temporal variability while they have opposite effects for primary producers. By considering nutrient cycling, this new model improves our understanding of the response of food webs to nutrient availability and opens perspectives to better link studies on food web dynamics and ecosystem functioning.

ecology↗