Biology subjects

Charles, C.

Publications and source records attributed to Charles, C..

7 recordsLinked to original sources

bioRxiv2026

First O-demethylation activity in Arabidopsis specialized metabolism resolves the missing step in esculetin biosynthesis

Coumarins are phenylpropanoid-derived specialized metabolites that contribute to plant defence, shape plant-microbe interactions in the rhizosphere, and promote iron acquisition. In Arabidopsis thaliana, a model plant for iron-responsive coumarin metabolism, the enzymatic origin of the catecholic coumarin esculetin has long remained unresolved. Here we identify the first O-demethylation reaction in Arabidopsis specialized metabolism and show that 2-oxoglutarate- and Fe(II)-dependent dioxygenases catalyze scopoletin 6-O-demethylation to form esculetin. We designate these enzymes scopoletin 6-O-demethylases (S6ODs) and validate their activity through biochemical characterization, together with metabolomic profiling and independent loss-of-function mutant lines providing genetic evidence in planta. Disruption of S6OD activity remodels coumarin profiles and alters plant performance under limited iron availability, indicating that esculetin biosynthesis contributes to plant responses under these conditions. Our findings resolve the long-sought missing step in esculetin biosynthesis. It establishes O-demethylation as a previously unrecognized reaction in Arabidopsis specialized metabolism and suggest that 2OGD-mediated O-demethylation is recurrently recruited during evolution of plant metabolism, with implications for metabolic engineering and improvement of iron acquisition traits in crops.

plant biology↗

bioRxiv2026

Prader-Willi syndrome genes are expressed in placenta and play a role in function

The neurodevelopmental disorder Prader-Willi syndrome (PWS) is caused by loss of paternally-derived gene expression from the imprinted interval on chromosome 15q11-q13. Recently, it has been suggested that the abnormal feeding-related behaviours characteristic of PWS may, in part, be developmentally programmed in utero via abnormal placental function. Here we report that several PWS-genes are expressed in mouse placenta with three PWS-transcripts Magel2, Necdin and the lncRNA Sngh14, co-localising to the Kdr-positive fetal endothelial cells of the labyrinth zone central to nutrient transport. In a novel PWS deletion mouse model (Large+/-) we find markedly reduced expression of PWS genes in the placenta and an associated [~]25% reduction in Kdr-positive fetal endothelial cells. Although this did not directly translate into a significant reduction in fetal growth late in gestation, these data suggest that placental function and nutrient transfer from mother to fetus could be compromised in PWS contributing to later post-natal phenotypes. Summary statementReduced expression of PWS-associated genes in the mouse placenta results in a 25% loss of the fetal endothelial cells that play a central role in nutrient and gas exchange.

physiology↗

bioRxiv2024

Glacier Retreat Effects On Ecosystem Development And Carbon Dynamics

One of the clearest indicators of global warming is the retreat of Alpine glaciers. Organisms rapidly colonize bare ground free from ice, and in less than a century complex ecosystems can develop in a process of primary succession, where community changes as terrain age increases and interactions within species change over time. When glaciers retreat the resulting ice-free soil is exposed to new forms of chemical and biological weathering, with initiating soil formation as an important driver of evolving ecosystems. Soils play an important role in the global carbon (C) cycle, serving as the largest reservoir of carbon. CO2 is removed from the atmosphere by plant photosynthesis, then stored in biomass and soils, and released again to the atmosphere via plant and soil respiration. Soil respiration includes CO2 production by heterotrophic soil organisms (e.g., bacteria, fungi, invertebrates) that metabolize plant litter and soil organic matter, and autotrophs (e.g. plant roots). However, little is known about the development of soils, their physico-chemical changes, and their influence on plant diversity and soil carbon emission (CO2) after glacier retreat. This study aims to investigate how the retreat of the Mont Mine and Ferpecle glaciers (Valais Alps, Switzerland) influences soil functioning and vegetation development. For this purpose, we carried out soil analyses and vegetation surveys on 5 ice-free stages deglaciated between 1864 and 2023. Soil physico-chemical properties (pH, soil organic matter, organic carbon and nitrogen, granulometry, available elements, total elements), soil CO2 respiration fluxes, and plant communities (composition, diversity, richness, biomass) were studied in 20 plots along the glacier forefield. Our results show that vegetation develops according to the principles of primary succession, going further from glacier front: from pioneer vegetation 7 years after glacier retreat, progressing through early vegetation at 20 years, then to intermediate vegetation, and ultimately culminating in a climax coniferous forest, 140 years after glacier retreat. Over 140 years, the increase in vegetation productivity results in a greater transfer of organic matter (SOM) to the soil, which increases organic carbon, nitrogen, and nutrient levels, and decreases pH values as it releases organic acids. Aboveground plant biomass (i.e. carbon storage) increases over the succession, however, plant diversity and richness peak at the intermediate stages and then level off due to the dominance of few species in the late stages. At the intermediate stage, there is also a peak observed in soil respiration (CO2 flux), which in turn promotes plant colonization and diversity. Thus, the soil, along with its development stages and properties, plays a critical role in carbon accumulation, leading to an increased potential for carbon release as organic matter storage increases. This project aims to contribute to the understanding of the consequences of global warming on recently deglaciated ecosystems, which remain still poorly overlooked.

ecology↗

bioRxiv2024

Adult lifespan effects on functional specialization along the hippocampal long axis

There has been increasing attention to differences in function along the hippocampal long axis, with the posterior hippocampus proposed to be well suited to representing fine-grained details and the anterior hippocampus having coarser representations. Whether long axis functional specialization persists into older age is not well understood, despite known age-related declines in the level of detail in memories. In this study, we used a large database of resting state fMRI data (n =322 humans of both sexes included) from across the adult lifespan (ages 18-88) to determine the degree of functional differentiation across the hippocampal posterior-anterior axis. Our first approach was to measure the similarity among signals within hippocampal subregions. We found that signals within the most posterior hippocampal subregion became more similar to one another in older age, but this effect did not relate to memory performance. As a second approach, we measured functional connectivity between hippocampal subregions and the rest of the brain. The functional connectivity profiles of the posterior and anterior hippocampal subregions became more distinct from one another with increasing age, driven by relative stability in anterior hippocampal functional connectivity but more significant age-related differences in posterior subregions of the hippocampus. Stronger connectivity between the anterior hippocampus and several cortical regions was associated with better memory performance in older adults, suggesting that maintenance of anterior hippocampal connectivity may help preserve episodic memory among high performing older adults.

neuroscience↗

bioRxiv2024

Using lineage-specific patterns to understand convergence of enzymatic functions led to the identification of Moraceae-specific P450s involved in furanocoumarin biosynthesis

O_LISpecialized metabolites are molecules involved in plants interaction with their environment. Elucidating their biosynthetic pathways is a challenging but rewarding task, leading to societal applications and ecological insights. Furanocoumarins emerged multiple times in Angiosperms, raising the question of how different enzymes evolved into catalyzing identical reactions. C_LIO_LITo identify enzymes producing lineage-specific metabolites, an evolutionary-based approach was developed and applied to furanocoumarin biosynthesis in Ficus carica (Moraceae). This led to the characterization of CYP71B129-131a, three P450 enzymes whose evolution of the function was investigated using phylogenetics, structural comparisons and site-directed mutagenesis. C_LIO_LICYP71B129 and CYP71B130,131a were found to hydroxylate umbelliferone (coumarin) and xanthotoxin (furanocoumarin), respectively. Results suggest that CYP71Bs xanthotoxin hydroxylase activity results from duplications and functional divergence of umbelliferone hydroxylase genes. Structural comparisons highlighted an amino acid affecting CYP71Bs substrate specificity, which may play a key role in allowing xanthotoxin hydroxylation in several P450 subfamilies. C_LIO_LICYP71B130-131a characterization validates the proposed enzyme-discovery approach, which can be applied to different pathways and help to avoid the classic bottlenecks of specialized metabolism elucidation. The CYP71Bs also exemplify how furanocoumarin-biosynthetic enzymes can stem from coumarin-biosynthetic ones and provides insights into the molecular mechanisms underlying the multiple emergences of xanthotoxin hydroxylation in distant P450 subfamilies. C_LI

plant biology↗

bioRxiv2023

Role of Adenosine Deaminase in Prostate Cancer Progression

Prostate cancer (PCa) is the second most common cancer and constitutes about 14.7% of total cancer cases. PCa is highly prevalent and more aggressive in African American (AA) men when compared to European-American (EA) men. PCa tends to be a highly heterogeneous malignancy with a complex biology that is not fully understood. We use metabolomics as a tool to understand the mechanisms behind PCa progression and disparities in its clinical outcome. A key enzyme in the purine metabolic pathway, Adenosine deaminase (ADA) was found upregulated in PCa. ADA was also associated with higher-grade PCa and poor disease-free survival. The inosine-to-adenosine ratio which is a surrogate for ADA activity was high in the urine of PCa patients and higher in AA PCa compared to EA PCa. To understand the significance of high ADA in PCa, we established ADA overexpression models and performed various in vitro and in vivo studies. Our studies have revealed that an acute increase in the expression of ADA during later stages of tumor development enhances in vivo growth in multiple pre-clinical models. Further analysis reveals that this tumor growth could be driven by the activation of mTOR signaling. Chronic ADA overexpression shows alterations in the cells adhesion machinery and a decrease in the adhesion potential of the cells to the extracellular matrix in vitro. Loss of cell-matrix interaction is critical for metastatic dissemination, suggestive of ADAs role in promoting metastasis. This is consistent with the association of higher ADA expression with higher-grade tumors and poor patient survival. Overall, our findings suggest that increased ADA expression may promote PCa progression, specifically tumor growth and metastatic dissemination.

cancer biology↗

bioRxiv2018

An interdisciplinary study around the reliquary of the late cardinal Jacques de Vitry

The reliquary of Jacques de Vitry, a prominent clergyman and theologian in the early 13th century, has experienced several transfers over the last centuries, which seriously question the attribution of the remains to the late Cardinal. Uncertainty about the year of his birth poses an additional question regarding his age at death in 1240. The reliquary, located in the Saint Marie dOigines church, Belgium, was reopened in 2015 for an interdisciplinary study around his relics as well as the Treasure of Oignies, a remarkable cultural heritage notably built from Jacques de Vitrys donation. Anthropological, isotopic and genetic analyses were performed independently on the remains found in the reliquary. Results of the analyses provided evidence that the likelihood that these remains are those of Jacques de Vitry is very high: the remains belong to the same human male individual and the historical tradition about his age is confirmed. In addition, a separate relic (left tibia) was analysed and found to match with the remains of the reliquary (right tibia). The unique Jacques de Vitrys mitre, made of parchment, was sampled non-destructively and the extracted parchment collagen was analysed by a proteomic method in order to determine the animal species. The results showed that, surprisingly, not all parts of the mitre were made from the same species. All together, these findings are expected to fertilize knowledge carried by historical tradition around the relics of Jacques de Vitry and his related cultural heritage.

genetics↗