Biology subjects

Delmas, C.

Publications and source records attributed to Delmas, C..

8 recordsLinked to original sources

bioRxiv2026

WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease

The aggregation of -synuclein (-SYN) into Lewy bodies (LBs) is a central event in the pathogenesis of Parkinsons disease (PD) and related synucleinopathies1,2. Despite significant advances in understanding -SYN self-assembly, the precise sequence of early aggregation steps has not been directly visualized in living neurons. Here, we use an optogenetic-induced protein aggregation system with a high temporal resolution to monitor the onset of -SYN assembly in neurons. We found that the initiation and accumulation of -SYN aggregates occur predominantly at the lysosomal membrane, an event driven by the -SYN N-terminus and modulated by the membrane-associated adaptor protein WD repeat-containing protein 44 (WDR44). Remarkably, we demonstrate that WDR44 knockdown markedly reduced de novo -SYN aggregation in both neuronal cultures and in vivo, whereas WDR44 overexpression enhances -SYN aggregation in PD patient-derived iPSC neurons. Consistent with its potential pathogenic involvement, WDR44 aberrantly accumulates in vivo and in the brains of PD patients, where it colocalizes with LB inclusions. Finally, we show that lysosome-associated -SYN aggregates compromised lysosomal structure and function, leading to neuronal impairment, a phenotype worsened by WDR44 overexpression, linking early aggregation events to downstream toxicity. Together, these findings reveal the earliest dynamic stages of -SYN oligomerization in living neurons and identify the WDR44--SYN interaction as a promising therapeutic target for reducing -SYN pathology and enabling early intervention in PD.

neuroscience↗

bioRxiv2026

Sequencing depth overcomes extraction bias: repurposing human WGS data for salivary microbiome profiling

Large-scale human genomic projects have generated whole-genome sequencing (WGS) data from hundreds of thousands of individuals, primarily to study host genetic variation. When saliva is the DNA source, the resulting datasets also contain microbial reads that are routinely discarded. Here, we investigate whether these host-centric WGS workflows can yield reliable microbiome profiles, effectively doubling the research value of existing data without additional sampling. We compared non-human reads from 39 deeply sequenced saliva samples from the GAZEL cohort (miG dataset; median [~]43 million reads/sample) with 14 samples processed with microbiome-optimized extraction (ASAL; median [~]4.3 million reads/sample), using two complementary classifiers: meteor, a coverage-based mapper against a curated saliva-specific database, and sylph, a k-mer classifier against the Genome Taxonomy Database (GTDB). Despite the absence of microbial lysis optimization, miG samples showed up to 3-fold higher species richness, [~]10-fold greater sequencing depth, and significantly lower inter-sample variability (PERMANOVA R{superscript 2} = 0.10, p = 0.001; BETADISPER p = 0.0036). Rarefaction to 10 reads eliminated most compositional differences, demonstrating that sequencing depth is the primary driver of community stability. Only [~]2% of detected taxa (12 of 592) showed extraction-related differences. The two classifiers exhibited fundamentally different depth-sensitivity profiles, with sylph retaining systematic detection asymmetries even after depth normalization, highlighting that classifier choice introduces biases that affect cross-study comparisons. These results show that biobank WGS data from saliva can be repurposed for robust, population-scale oral microbiome analyses, enabling simultaneous investigation of host genomic variation and the microbiome from the same archived samples. ImportanceSaliva-based whole-genome sequencing datasets generated across various cohorts to study human genetics contain non-human reads that are routinely discarded, thereby overlooking valuable microbial information. We show that these reads are sufficient to reconstruct robust oral microbiome profiles -- without any additional sampling or laboratory work. This finding unlocks a vast archive of existing genomic data for retrospective microbiome research, enabling population-scale studies of oral microbial diversity, host-microbiome interactions, and disease associations at minimal additional cost. We further demonstrate that the choice of taxonomic classifier introduces systematic, depth-dependent biases that persist even after normalization, a practical consideration for any cross-cohort or multi-platform microbiome study.

genomics↗

bioRxiv2026

A plant-based biostimulant modulates grapevine susceptibility within a realistic water stress window through priming and phenylpropanoid pathway regulation

Fluctuating extreme weather events, coupled with rising average temperatures, can severely impact grapevine physiology and yield. While biostimulants have been gaining acceptance as a short-terms tools to enhance grapevine resilience, their adoption is hindered by inconsistent efficacy, partly driven by unpredictable plant stress levels. Over two contrasting seasons, we integrated physiological, transcriptomic, and metabolomic analyses to investigate how a plant-based biostimulant modulates the sensibility of Vitis vinifera under varying intensities of heat, drought, and their combination. This panel of water status, ranging from -0.02 to -1.6 MPa, revealed that the physiological response induced by the biostimulant treatment alleviates water stress within a field-relevant hydraulic window located between -0.4 and -1.2 MPa. Moreover, moderate but constitutive reduction of growth parameters in biostimulant plants, suggests a trade-off between vegetative development and abiotic stress responses. Accordingly, gene expression analysis revealed an interaction between water availability and the plant response to the biostimulant, which suggest an activation of priming mechanisms. Metabolic profiling supported these findings, highlighting the central role of phenylpropanoid pathway modulation, together with adjustments in ROS dynamics and stress-related hormone responses, particularly abscisic acid. Overall, this work emphasizes the need for integrating detailed plant water status and leaf gas exchange to accurately evaluate biostimulant performances under abiotic stress.

plant biology↗

bioRxiv2025

Wood composition, rather than microbial communities, underpins varietal differences in wood degradation and esca foliar symptom expression in grapevine

Deciphering the interplay between microbial communities and host defence mechanisms is key to understanding plant health. In perennial plants, the balance between endophytes and wood (i.e. secondary xylem) defence responses governs wood degradation and vascular disease expression. Esca is a complex vascular disease contributing to grapevine decline, with an incidence variable across cultivars but the mechanisms underlying its expression and varietal susceptibility remain unclear. We assessed relationships between internal wood degradation and esca foliar symptoms in Vitis vinifera L. cultivars grown in a common garden, and, at the cultivar level, we tested for correlations between (i) susceptibility to wood decay and esca expression (n = 16 cultivars) and (ii) wood biochemical traits, and healthy wood endophytic microbial communities (n = 23 cultivars). Unlike other types of necrosis, white-rot necrotic wood was significantly more abundant in plants that had expressed esca leaf symptoms in previous years, particularly in the most susceptible cultivars. These cultivars also contained significantly lower levels of constitutive wood extractives. However, glycosylated phenylpropanoids accumulated in the wood of esca-symptomatic plants, especially in highly susceptible cultivars. By contrast, esca expression and varietal susceptibility had only a marginal effect on the diversity, composition and putative functions of microbial communities in healthy wood. They did not influence either the relative abundance of Fomitiporia mediterranea, the putative causal agent of white-rot in grapevine. Esca susceptibility appears primarily linked to wood degradability and metabolic responses, rather than healthy wood's microbial communities, suggesting that the use of less susceptible varieties together with white-rot removal might attenuate grapevine decline.

plant biology↗

bioRxiv2025

Differential impacts of drought and esca expression on Ascomycota fungi in the trunks and young organs of mature grapevines

Perennial plant decline is increasingly threatening the profitability and sustainability of agriculture and forestry worldwide. It results from intricate interactions between microbial communities, the plant host, and abiotic stressors. We investigated the effects of drought and esca disease on mature grapevine phytobiomes. Grapevines display no esca leaf symptoms during droughts, but the impacts of drought and esca expression on fungal communities and wood health in mature plants remain poorly understood. We studied 43 uprooted 30-year-old naturally infected vines in three experimental conditions: well-watered asymptomatic (Control) vines, vines with esca symptoms (Esca), and vines subjected to water deficit (WD) over two consecutive summers. We profiled trunk, cane, stem and petiole Ascomycota communities by DNA metabarcoding with primers specifically designed for grapevine trunk-associated Ascomycota, and quantified wood necrosis. The Ascomycota communities of trunks and younger organs clearly differed, and drought and esca had different impacts on the Ascomycota communities of perennial and young organs. In the trunk, drought significantly decreased fungal diversity in healthy wood and increased the abundance of wood pathogens (e.g. Phaeomoniella chlamydospora, Botryosphaeria dothidea). In young organs, esca expression decreased the species richness and diversity of the Ascomycota community to a greater extent than drought. We also found that the relative proportion of healthy wood was smaller in plants with esca symptoms than in control plants. Thus, drought increased Ascomycota pathogen abundance in the trunk but did not increase wood degradation and esca expression, highlighting the need to investigate the molecular basis of plant-microbiome interactions under multi-stress conditions.

plant biology↗

bioRxiv2024

Genome analysis of the esca-associated Basidiomycetes Fomitiporia mediterranea, Fomitiporia polymorpha, Inonotus vitis, and Tropicoporus texanus reveals virulence factor repertoires characteristic of white-rot fungi

Some Basidiomycete fungi are important plant pathogens, and certain species have been associated with the grapevine trunk disease esca. We present the genomes of four species associated with esca: Fomitiporia mediterranea, Fomitiporia polymorpha, Tropicoporus texanus, and Inonotus vitis. We generated high-qualityphased genome assemblies using long-read sequencing. The genomic and functional comparisons identified potential virulence factors, suggesting their roles in disease development. Similar to other white-rot fungi known for their ability to degrade lignocellulosic substrates, these four genomes encoded a variety of lignin peroxidases and carbohydrate-active enzymes (CAZymes) such as CBM1, AA9, and AA2. The analysis of gene family expansion and contraction revealed dynamic evolutionary patterns, particularly in genes related to secondary metabolite production, plant cell wall decomposition, and xenobiotic degradation. The availability of these genomes will serve as a reference for further studies of diversity and evolution of virulence factors and their roles in esca symptoms and host resistance.

genomics↗

bioRxiv2021

Neurexins Regulate GABA Co-release by Dopamine Neurons

Midbrain dopamine (DA) neurons are key regulators of basal ganglia functions. The axonal domain of these neurons is highly complex, with a large subset of non-synaptic release sites and a smaller subset of synaptic terminals from which glutamate or GABA are released. The molecular mechanisms regulating the connectivity of DA neurons and their neurochemical identity are unknown. Here we tested the hypothesis that the trans-synaptic cell adhesion molecules neurexins (Nrxns) regulate DA neuron neurotransmission. Conditional deletion of all Nrxns in DA neurons (DAT::Nrxns KO) showed that loss of Nrxns does not impair the basic development and ultrastructural characteristics of DA neuron terminals. However, loss of Nrxns caused an impairment of DA transmission revealed as a reduced rate of DA reuptake following activity-dependent DA release, decreased DA transporter levels, increased vesicular monoamine transporter expression, and impaired amphetamine-induced locomotor activity. Strikingly, electrophysiological recording revealed an increase of GABA co-release from DA neuron axons in the striatum of the KO mice. These findings suggest that Nrxns act as key regulators of DA neuron connectivity and DA-mediated functions. HighlightsO_LIThe study provides the first direct evidence of the role of neurexins in dopaminergic neurons. C_LIO_LIThe synaptic adhesion molecules, neurexins, are not required for maintaining the structure of dopamine neuron terminals. C_LIO_LINeurexins regulate dopaminergic neurotransmission through regulation of dopamine reuptake, impacting amphetamine-induced locomotion. C_LIO_LIDeletion of Nrxns in DA neurons causes a region-specific increase of GABA release by DA neurons. C_LI

neuroscience↗

bioRxiv2020

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replicates. We also investigated the potential of characterising individual salivary microbiomes from non-human DNA fragments found in saliva. We observed the majority of discordant genotype calls between blood and saliva calls fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individuals blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project. Author SummaryDNA is usually collected from blood for the analysis of human genomes. In France, a new and very large genetic dataset will be created where selected participants will be sent saliva-collection kits in the post as this data collection method presents numerous logistical benefits. It has been previously shown that good quality genetic data can be created from saliva, though existing studies have often not considered the latest technologies or have only analysed a very small number of individuals. In this study, we have analysed genetic data derived from saliva for 39 individuals to give a firm conclusion that the proposed genome sequencing approach of the new French dataset will be capable of provided high quality data by making a comparison to pre-existing genetic data derived from blood for these 39 individuals. In order to do so, we developed a novel method (presented here) to establish the similarity between two sets of genetic data for the same individual that are generated from separate DNA samples. Finally, we have also demonstrated an added bonus of colleting saliva samples: that it is possible to gather both human genetic data and potentially interesting salivary microbiome data at the same time by separating and analysing in parallel human and non-human DNA fragments.

genetics↗