Biology subjects

Couture, C.

Publications and source records attributed to Couture, C..

14 recordsLinked to original sources

bioRxiv2026

Adipose Tissue Pericellular Fibrosis, Weight Loss and Features of Metabolic Dysfunction-Associated Steatotic Liver Disease after Bariatric Surgery

Introduction: Adipose tissue fibrosis has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and suboptimal weight loss after bariatric surgery. The objective was to characterize changes in adipose tissue fibrosis and extracellular matrix (ECM) components in adipose tissues from two abdominal fat compartments, subcutaneous and omental, in response to bariatric surgery; and determine the effect of weight loss on the association between adipose tissue fibrosis and MASLD feature changes with weight loss. Methods: Liver and adipose tissue biopsy samples were obtained before and after weight loss from patients who underwent two-stage bariatric surgery. Adipose tissue pericellular fibrosis was evaluated histologically with picrosirius red staining for collagen quantification and normalized to adipocyte count per microscope field. Transcript levels of ECM remodeling and inflammatory genes were measured by RNA sequencing in subcutaneous adipose tissue pre- and post-surgery. Results: At baseline, adipose tissue pericellular fibrosis did not associate with MASLD features, metabolic dysfunction-associated steatohepatitis or hepatic fibrosis in patients with severe obesity. Changes in liver histology after surgery were unrelated to changes in adipose tissue fibrosis. Transcripts for most genes involved in ECM remodeling and inflammation were downregulated in subcutaneous fat one year after bariatric surgery. Omental, but not subcutaneous, adipose tissue fibrosis decreased after surgery when adjusted for cell number (mean {+/-} SD: 0.41 {+/-} 0.12 vs 0.32 {+/-} 0.08 {micro}m2/cell, p<0.005). Higher subcutaneous adipose tissue fibrosis correlated with reduced weight loss (estimate {+/-} SE: -2.04 {+/-} 0.99, p<0.05) and BMI loss (-0.73 {+/-} 0.35, p<0.05), while increased omental adipose tissue fibrosis after weight loss was associated with worsening hepatic fibrosis (0.31 {+/-} 0.14, p<0.05). Conclusion: In individuals with severe obesity undergoing bariatric surgery, adipose tissue fibrosis is poorly correlated with MASLD features. Notably, pericellular fibrosis in subcutaneous abdominal, but not omental, adipose tissue was associated with a reduced weight-loss response to surgery.

physiology↗

bioRxiv2026

Decoding causal genes and programs from regulatory variants in aortic valve disease

Aortic valve disease is common, yet its regulatory mechanisms remain poorly understood. We performed multi-omic profiling of human aortic valve interstitial cells (HAVICs), identifying 11,891 allele-specific chromatin accessibility QTLs (as-caQTLs), 48% novel to this cell type. These variants were enriched in active enhancers, disrupted transcription factor (TF) motifs, particularly AP-1, TEAD and GATA families, and were validated by allele-specific TF binding assays. A fine-tuned deep DNA sequence model prioritized common and rare variants at risk loci predicted to impact chromatin accessibility. Single-cell CRISPRi perturbation of 247 variants identified cis-target genes at 55 as-caQTL elements, including loci without eQTLs. We demonstrate that common regulatory variants controlling elastin and fibrillin impact the development of the aortic valve apparatus. We provide genetic evidence and a mechanistic framework for the contribution of a reduced aortic root size to CAVD risk. Perturbations identified core cell programs led by upstream regulators AHNAK, PDIA6, and RNFT1 converging on extracellular matrix production and iron transport.

genetics↗

bioRxiv2026

Optimizing light environment enables speed breeding in forage legumes: physiological limits and generation time reduction in Medicago sativa and Medicago truncatula

Climate change and increasing global demand for animal products are intensifying the need to accelerate genetic improvement of forage crops. Speed breeding (SB) has emerged as a powerful tool to shorten generation cycles; however, its application in perennial and autotetraploid forage legumes remains limited, particularly regarding reproductive performance and physiological constraints. Here, we optimized photoperiod, light intensity, and light quality to accelerate the life cycle of Medicago sativa (alfalfa) and its diploid relative Medicago truncatula under controlled conditions. We evaluated flowering, fruiting, seed harvest time, seed set, and germination across independent and combined SB treatments, and assessed photosynthetic performance to identify potential physiological trade-offs. Blue- red light supplementation, moderate-to-high irradiance (450 {micro}mol m-2 s-1), and extended photoperiods significantly accelerated reproductive development in both species, although optimal combinations differed between the diploid and autotetraploid backgrounds. A combined SB regime (20/4 h photoperiod at 450 {micro}mol m-2 s-1) reduced time to harvest by 17% in M. sativa and 28% in M. truncatula, while maintaining viable seed production. Chlorophyll fluorescence analysis revealed a higher photosynthetic plasticity in alfalfa compared with M. truncatula, indicating species-specific physiological limits to SB intensification. Our results establish practical SB conditions for alfalfa and an agronomically relevant M. truncatula genotype, providing an enabling platform to accelerate breeding cycles and trait evaluation in forage legumes.

plant biology↗

bioRxiv2025

A rapid and accurate PCR-based method for mating-type determination in the heterothallic oomycete Plasmopara viticola, the causal agent of grapevine downy mildew

Plasmopara viticola is a heterothallic diploid oomycete responsible for grapevine downy mildew, one of the most damaging grapevine diseases worldwide. Since no rapid method for mating type characterization of strains is currently available, mating type identification must be performed through crossing assays, which are time-consuming. This study reports the development of two PCR-based molecular markers (MT_indel1 and MT_indel2) based on size variation to distinguish between the mating-type alleles of the oomycete Plasmopara viticola. For both markers, P1 strains (Mat-a/Mat-b) exhibited a double-band profile, whereas P2 strains (Mat-a/Mat-a) displayed a single PCR band. The markers were validated on a set of 37 reference strains collected across Europe and showed perfect concordance with mating-type phenotypes determined by crossing tests. They provide a robust, sensitive, and inexpensive DNA-based detection system for mating-type identification in P. viticola, offering valuable insights into the pathogens reproductive biology and genetic diversity.

molecular biology↗

bioRxiv2025

A multivirulent Plasmopara viticola strain from Cilaos on Reunion Island breaks down Rpv1, Rpv3.1 and Rpv10 mediated resistance of grapevine

AbstractGrapevine downy mildew, caused by Plasmopara viticola, is one of the most destructive diseases in viticulture. Resistance-based management strategies rely on grapevine varieties carrying major resistance loci (Rpv). Although breakdown of several loci has been reported, Rpv1 had remained effective until now. Here, we provide the first evidence of Rpv1 breakdown by P. viticola in Cilaos on Reunion Island (France) and the first case of a strain simultaneously overcoming three resistances of grapevine. We combined pathogenicity assays with whole-genome sequencing to characterize a P. viticola strain collected in Cilaos in 2023, alongside a panel of eight reference strains of known virulence. Hypersensitive response and sporulation were assessed for each strain on Chardonnay (susceptible variety) and four resistant varieties carrying Rpv1, Rpv3.1, Rpv10, or Rpv12. The strain collected in Cilaos was able to overcome not only Rpv1 but also Rpv3.1 and Rpv10. On Rpv1, we observed a complete loss of host recognition with high sporulation. On Rpv3.1, the phenotype was consistent with previous breakdowns, and the strain carried the vir1 allele previously described in France. By contrast, the breakdown of Rpv10 differed from that reported in European populations: whereas European strains displayed only partial breakdown of resistance, the strain of Cilaos showed complete loss of host recognition with high sporulation. Moreover, genomic analyses revealed a novel mutation, a large homozygous deletion in the corresponding avr locus. Our genomic data analyses further suggests that this P. viticola strain shares a genetic background with populations from mainland France, raising serious concerns about the potential emergence and spread of multivirulent lineages in Europe. These findings highlight the need for large-scale virulence monitoring of P. viticola and improved strategies for the sustainable management of grapevine resistance in Europe.

plant biology↗

bioRxiv2025

Seasonal changes in the physiology and metabolism of grapevine perennating buds

Grapevine (Vitis vinifera L.) buds undergo seasonal dormancy to survive unfavourable conditions and synchronize growth with environmental cues. While dormancy transitions have been widely studied in temperate woody perennials, the physiological and metabolic dynamics underlying these transitions in grapevine remain poorly understood. Our study investigates seasonal changes in the physiology and metabolism of perennating buds in V. vinifera cv. Cabernet Sauvignon, focusing on dormancy depth, respiration, sugar metabolism, and cell cycle activity. We identified three distinct phases of bud quiescence: (i) para-dormancy (early summer), characterized by active metabolism and high levels of tricarboxylic acid cycle intermediates, shikimate, and myo-inositol; (ii) endo-dormancy (late summer to autumn), where dormancy depth peaked in late summer and was marked by reduced respiration and bud water content, and a sharp decline in hexose levels with a concomitant increase in raffinose; and (iii) eco-dormancy (winter to spring), featuring increased respiration, sugar mobilization (notably sucrose, glucose, and trehalose), and reactivation of cell division, with a shift of cells into the G2 phase. Just prior to bud burst, we observed a significant accumulation of sugar-phosphates, providing evidence that supports their role in promoting bud burst also in grapevine. Our findings provide new insights into the biochemical and physiological regulation of bud dormancy and bud burst, contributing to a deeper understanding of dormancy transitions in perennial crops.

plant biology↗

bioRxiv2025

Liquid-phase determination of Arabidopsis respiration and photosynthesis using Clark-type O2 electrodes

Photosynthesis and respiration are fundamental metabolic processes in plants, tightly connected through shared substrates, energy dynamics, and redox balance. Arabidopsis is the key genetic model for plants but monitoring these sorts of physiological processes presents significant challenges using traditional gas-exchange or fluorescence-based techniques due to the small size of intact Arabidopsis thaliana (arabidopsis) seedlings. Here, we validate and characterize the use of Clark-type oxygen electrodes, specifically the Hansatech Oxytherm+P system, to quantify both photosynthetic and respiratory activity in intact arabidopsis seedlings. By monitoring oxygen evolution in dark and light phases, we demonstrate that oxygen consumption and production correspond to mitochondrial respiration and photosynthesis, respectively. These processes were modulated by tissue biomass, light intensity, developmental stage, and stress conditions. Specific inhibitors such as potassium cyanide and paraquat confirmed that the recorded changes in oxygen concentrations reflected mitochondrial cytochrome oxidase activity and photosystem electron transport-dependent oxygen production, respectively. Moreover, oxygen evolution increased significantly with bicarbonate supplementation, validating the systems sensitivity to carbon fixation. We further showed that photosynthetic activity measured with this method correlates with a quantitative green index and responds dynamically to de-etiolation, abiotic stress (salt, osmotic, oxidative), and temperature shifts. Our study lays the groundwork for measuring photosynthesis based on oxygen evolution and respiration in arabidopsis knockout mutants, CRISPR lines, overexpression lines and ecotypes using Clark-type oxygen electrodes and highlights key considerations and limitations to consider when applying this approach. This platform could also be adapted for many other small tissue plant samples.

plant biology↗

bioRxiv2025

Influenza A Virus Interferes With Respiratory Syncytial Virus in Mice and Reconstituted Human Airway Epithelium

Epidemiological studies suggest that respiratory syncytial virus (RSV) and influenza A virus (IAV) might interfere with each other. Viral interference mainly relies on interferon production elicited by a first virus that reduces the replication of a second virus. In this paper, we first investigated the interactions between RSV-A2 and influenza A(H1N1)pdm09 in BALB/c mice infected with each single virus or both viruses simultaneously or sequentially before, at the peak of interferon elicited by each virus or after that peak. IAV reduced by almost 3.0 logs the replication of RSV administered at the peak of interferon induced by influenza, but the opposite was not true. However, IAV-infected mice challenged with RSV or the vehicle lost more weight and had a lower survival rate compared to single infections. Interferon expression, cytokine levels and pulmonary inflammation were almost similar between groups. Disease worsening was attributed to an aggravation of IAV-induced pulmonary congestion following intranasal instillation of fluid (with or without RSV). In human airway epithelia, IAV also interfered with RSV replication. Viral interference was dependent on the timing and sequence of infections, but not on differential interferon susceptibilities. Overall, our results help to understand the mechanisms of interaction between two major respiratory viruses. ImportanceRespiratory syncytial virus and influenza virus may interfere with each other based on epidemiological studies. It is suggested that a first virus may induce the production of interferon and interfere with the replication of a second unrelated virus. Our data showed that influenza A virus interferes with respiratory syncytial virus replication in mouse lungs, but the opposite was not observed. In reconstituted human airway epithelia, viral interference was dependent on the timing and sequence of infections, but not on differential interferon susceptibilities. Understanding the mechanisms of interaction between respiratory viruses may help the development of prophylactic or therapeutic modalities.

microbiology↗

bioRxiv2024

Recombination landscape and karyotypic variations revealed by linkage mapping in the grapevine downy mildew pathogen Plasmopara viticola

Plasmopara viticola, the causal agent of grapevine downy mildew, is a biotrophic oomycete engaged in atight coevolutionary relationship with its host. Rapid adaptation of the pathogen is favored by annual sexual reproduction which generates genotypic diversity. With the aim of studying the recombination landscape across the P. viticola genome, we generated two half-siblings F1 progenies (N=189 and 162). Offspring were genotyped by targeted sequencing of a set of 5,000 informative SNPs. This enabled the construction of unprecedented high-density linkage maps for this species. The reference genome could be assembled into 17 pseudo-chromosomes, anchoring 88% of its physical length. We observed a strong collinearity between parental genomes and extensive synteny with the downy mildew Peronospora effusa. In the consensus map, the median recombination rate was 13.8 cM/Mb. The local recombination rate was highly variable along chromosomes and recombination was suppressed in putative centromeric regions. Recombination rate was found negatively correlated with repeats coverage and positively correlated with gene coverage. However, genes encoding secreted proteins and putative effectors were under-represented in highly recombining regions. In both progenies, about 5% of the individuals presented karyotypic anomalies. Aneuploidies and triploidies almost exclusively originated from the male-transmitted chromosomes. Triploids resulted from fertilization by diploid gametes, but also from dispermy. Obligatory sexual reproduction each year may explain the lower level of karyotypic variation in P. viticola compared to other oomycetes. The linkage maps will be useful to guide future de novo chromosome-scale assemblies of P. viticola genomes and to perform forward genetics. SummarySexual reproduction contributes to the rapid adaptation of plant pathogens thanks to the recombination of genetic variants. By crossing strains of grapevine downy mildew, we built a set of linkage maps and describe the recombination landscape along the 17 chromosomes of the genome. The recombination rate varied greatly and was higher in gene-rich regions, but not in effector-rich regions. We observed an abnormal number of chromosomes in 5% of the offspring, which was mostly due to the male parent.

genetics↗

bioRxiv2023

An effector deletion leads to the breakdown of partial grapevine resistance to downy mildew

Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is a globally destructive disease that particularly affect the Eurasian wine grape V. vinifera. While genetically resistant varieties are becoming more accessible, populations of P. viticola are demonstrating rapid adaptability, successfully over-coming these resistances. Here we aimed to identify the avirulence genes involved in the interaction with the Rpv3.1-mediated resistance in grapevine. We sequenced the full genome of 136 P. viticola strains sampled in a natural population of Bordeaux (France) and characterized their development on both resistant and sensitive cultivars. The genome-wide association study allowed the identification of a genomic region associated with the breakdown of Rpv3.1 grapevine resistance (avrRpv3.1 locus). A diploid-aware reassembly of the P. viticola INRA-Pv221 genome allowed to detect structural variations in this locus, including a major 30 Kbp deletion. At the avrRpv3.1 locus, virulent P. viticola strains presented deletion on both haplotypes indicating that avirulence is recessive. The deletion involves two closely-related genes that encode proteins containing 800-900 amino acids with a signal peptide. The structure of the predicted proteins contains repeats of the LWY-fold structural modules, typical of oomycete effectors. Moreover, when these proteins were transiently expressed, they induced cell death in grapevines carrying Rpv3.1 resistance, confirming their avirulence nature. The first description of candidate effectors of P. viticola involved in the interaction with resistance gene provides valuable insights into the genetic mechanisms that enable P. viticola to adapt to grapevine resistance, laying a foundation for developing strategies to manage this damaging crop pathogen.

evolutionary biology↗

bioRxiv2020

Identification of the first oomycete mating-type locus sequence in the grapevine downy mildew pathogen, Plasmopara viticola

Mating types are self-incompatibility systems that promote outcrossing in plants, fungi and oomycetes. Mating-type genes have been widely studied in plants and fungi, but have yet to be identified in oomycetes, eukaryotic organisms closely related to brown algae that cause many destructive animal and plant diseases. We identified the mating-type locus of Plasmopara viticola, the oomycete responsible for grapevine downy mildew, one of the most damaging grapevine diseases worldwide. Using a genome-wide association approach, we identified a 570 kb repeat-rich non-recombining region controlling mating types, with two highly divergent alleles. We showed that one mating type was homozygous, whereas the other was heterozygous at this locus. The mating-type locus encompassed 40 genes, including one encoding a putative hormone receptor. Our findings have fundamental implications for our understanding of the evolution of mating types, as they reveal a unique determinism involving an asymmetry of heterozygosity, as in sex chromosomes and unlike other mating-type systems. This identification of the mating-type locus in such an economically important crop pathogen also has applied implications, as outcrossing facilitates rapid evolution and resistance to harsh environmental conditions.

evolutionary biology↗

bioRxiv2019

Strain-dependent impact of G and SH deletions provide new insights for live-attenuated HMPV vaccine development

Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75.\n\nThe {Delta}SH and {Delta}G deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the {Delta}G-85473 and especially {Delta}SH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system.

microbiology↗

bioRxiv2019

Long-Term Exposure to Elevated Lipoprotein(a) Levels, Parental Lifespan and Risk of Mortality

BackgroundElevated Lipoprotein(a) (Lp[a]) levels are associated with a broad range of atherosclerotic cardiovascular diseases (CVD). The impact of high Lp(a) levels on human longevity is however controversial. Our objectives were to determine whether genetically-determined Lp(a) levels are associated with parental lifespan and to assess the association between measured and genetically-determined Lp(a) levels and long-term all-cause and cardiovascular mortality.\n\nMethodsWe determined the association between a genetic risk score of 26 single nucleotide polymorphisms weighted for their impact on Lp(a) levels (wGRS) and parental lifespan (at least one long-lived parent; father still alive and older than 90 or fathers age of death [≥]90 or mother still alive and older than 93 or mothers age of death [≥]93) in 139,362 participants from the UK Biobank. A total of 17,686 participants were considered as having high parental lifespan. We also investigated the association between Lp(a) levels and all-cause and cardiovascular mortality in 18,720 participants from the EPIC-Norfolk study.\n\nResultsIn the UK Biobank, increases in the wGRS (weighted for a 50 mg/dL increase in Lp(a) levels) were inversely associated with a high parental lifespan (odds ratio=0.92, 95% confidence interval [CI]=0.89-0.94, p=2.7x10-8). During the 20-year follow-up of the EPIC-Norfolk study, 5686 participants died (2412 from CVD-related causes). Compared to participants with Lp(a) levels <50 mg/dL, those with Lp(a) levels [≥]50 mg/dL had an increased hazard ratio (HR) for all-cause (HR=1.17, 95% CI=1.08-1.27) and cardiovascular (HR=1.54, 95% CI=1.37-1.72) mortality. Compared to individuals with Lp(a) levels below the 50th percentile of the Lp(a) distribution (in whom event rates were 29.8% and 11.3%, respectively for all-cause and cardiovascular mortality), those with Lp(a) levels equal or above the 95th percentile of the population distribution ([≥]70 mg/dL) had HRs of 1.22 (95% CI=1.09-1.37, event rate 37.5%) and 1.71 (95% CI=1.46-2.00, event rate 20.0%), for all-cause mortality and cardiovascular mortality, respectively.\n\nConclusionsResults of this study suggest a potentially causal effect of Lp(a) on human longevity, support the use of parental lifespan as a tool to study the genetic determinants of human longevity, and provide a rationale for a trial of Lp(a)-lowering therapy in individuals with high Lp(a) levels.

genetics↗

bioRxiv2018

A high-quality grapevine downy mildew genome assembly reveals rapidly evolving and lineage-specific putative host adaptation genes

Downy mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high continuity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant-pathogen interactions. Pl. viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species.\n\nDATA AVAILABILITYRaw reads and genome assemblies have been deposited in GenBank (BioProjects PRJNA329579 for Pl. viticola and PRJNA448661 for Pl. muralis). Genome assemblies, gene annotations and analysis files (e.g. orthology relationships, full tables for GO enrichment analyses, pairwise dN/dS values and branch-site tests) have been deposited in Dataverse (Pl. viticola assembly and annotation: doi.org/10.15454/4NYHD6, Pl. muralis assembly and annotation: doi.org/10.15454/Q1QJYK, analysis files: doi.org/10.15454/8NZ8X9). Links to the data and information about the grapevine downy mildew genome project can be found at http://grapevine-downy-mildew-genome.com/.

genomics↗