Biology subjects

Menard, D.

Publications and source records attributed to Menard, D..

12 recordsLinked to original sources

bioRxiv2026

Identifying and engineering the molecular origins of lignin color for predictive staining of plant tissues.

Lignins in plant biomass are carbon-negative aromatic biopolymers which hold tremendous potential as multipurpose resources for sustainable bioeconomy, limited only by their chemical heterogeneity. Plant lignified tissues, such as sapwood and seed coats, vary in colors within and between species, indicating that specific lignin topochemistries determine the different colors. Yet, the responsible lignin chromogen(s) are unknown. We developed chemical imaging using UV-Vis microspectroscopy to link lignin color to topochemistry in isolates and plant samples. Using synthetic and technical lignins, we identified the different stable chromogens as homomeric lignin substructures varying in size, unit chemistry and interunit linkages. We controlled the accumulation of specific lignin chromogens using genetic engineering to similarly stain lignified tissues from different plant species. We established plant tissue engineering to cast plant tissues with pre-determined color by adjusting lignin topochemistries. We proved that biotechnological manipulation of the identified lignin chromogens predictably and stably stains lignified plant tissues.

bioengineering↗

bioRxiv2024

Gametocyte production and transmission fitness of African and Asian Plasmodium falciparum isolates with differential susceptibility to artemisinins

The emergence of Plasmodium falciparum parasites partially resistant to artemisinins (ART-R) poses a significant threat to recent gains in malaria control. ART-R has been associated with PfKelch13 (K13) mutations, which differ in fitness costs. This study investigates the gametocyte production and transmission fitness of African and Asian P. falciparum isolates with different K13 genotypes across multiple mosquito species. We tested three ART-sensitive (ART-S) isolates (NF54, NF135, NF180) and three ART-R isolates (ARN1G, 3815, PAT-023) for sexual conversion and transmission to Anopheles stephensi, An. gambiae and An. coluzzii. ART-R levels were quantified in vitro using the Ring-stage Survival Assay (RSA), and the transmission-reducing effects of dihydroartemisinin (DHA) on mature gametocytes were assessed. Results showed that ART-S parasite lines consistently produced gametocytes and transmitted effectively in all three mosquito species. ART-R isolates showed variability: ARN1G maintained high transmission levels, whereas 3815 showed limited transmission potential despite higher sporozoite loads in An. coluzzii. The African ART-R isolate PAT-023 demonstrated low gametocyte commitment but was transmitted efficiently in both An. gambiae and An. coluzzii. DHA exposure reduced mosquito infectivity for all isolates, regardless of K13 genotype. These findings, based on a limited number of field isolates, suggest that ART-R parasites remain transmissible across different Anopheles species. However, ART-R does not appear to confer a direct transmission advantage. This study highlights the complexity of ART-R dynamics and underscores the need for further research to inform malaria control strategies in regions where ART-R parasites are circulating.

microbiology↗

bioRxiv2023

Remote sensing of emperor penguin abundance and breeding success

Emperor penguins (Aptenodytes forsteri) are under increasing environmental pressure. Monitoring colony size and trends of this Antarctic seabird relies primarily on satellite imagery recorded near the end of the breeding season, when illumination levels are sufficient to capture images, but colony occupancy is highly variable. To correct population estimates for this variability, we develop a phenological model that accurately predicts the number of breeding pairs and fledging chicks, as well as key phenological events such as arrival, hatching and foraging times, from as few as six data points from a single season. The ability to extrapolate occupancy from sparse data makes the model particularly useful for monitoring remotely sensed animal colonies where ground-based population estimates are very rare or unavailable. TeaserThe Emperor penguin becomes the Southern Oceans canary in a coal mine through remote sensing its annual breeding success.

ecology↗

bioRxiv2022

Different combinations of laccase paralogs non-redundantly control the lignin amount and composition of specific cell types and cell wall layers in Arabidopsis

Vascular plants reinforce the cell walls of the different xylem cell types with lignin, a phenolic polymer. Specific lignin chemistries are conserved between the cell wall layers of each cell type to support their functions. Yet the mechanisms controlling the tight spatial localisation of specific lignin chemistries remain unclear. Current hypotheses focus on a control by monomer biosynthesis and/or export, while their cell wall polymerisation is viewed as random and non-limiting. Here we show that cell wall polymerisation using combinations of multiple different laccases (LACs) non-redundantly and specifically control the lignin chemistry in different cell types and their distinct cell wall layers. We dissected the roles of Arabidopsis thaliana LAC4, 5, 10, 12 and 17 by generating quadruple and quintuple loss-of-function mutants. Different combinatory loss of these LACs lead to specific changes in lignin chemistry affecting both residue ring structures and/or aliphatic tails in specific cell types and cell wall layers. We moreover showed that the LAC-mediated lignification had distinct functions in specific cell types. Altogether, we propose that the spatial control of lignin chemistry depends on different combinations of LACs with non-redundant activities immobilised in specific cell types and cell wall layers.

plant biology↗

bioRxiv2022

Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target

The uptake and digestion of host hemoglobin by malaria parasites during blood stage growth leads to significant oxidative damage of membrane lipids. Repair of lipid peroxidation damage is crucial for parasite survival. Here, we demonstrate that Plasmodium falciparum imports a host antioxidant enzyme, peroxiredoxin 6 (PRDX6), during hemoglobin uptake from the red blood cell cytosol. PRDX6 is a lipid peroxidation repair enzyme with phospholipase A2 (PLA2) activity. Inhibition of PRDX6 with a PLA2 inhibitor, Darapladib, increases lipid peroxidation damage in the parasite and disrupts transport of hemoglobin-containing vesicles to the food vacuole, causing parasite death. Furthermore, inhibition of PRDX6 synergistically reduces the survival of artemisinin-resistant parasites following co-treatment of parasite cultures with artemisinin and Darapladib. Thus, PRDX6 is a unique host-derived drug target for development of antimalarial drugs that could help overcome artemisinin resistance. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

cell biology↗

bioRxiv2021

Specific and dynamic lignification at the cell-type level controls plant physiology and adaptability

The biopolymer lignin, deposited in the cell walls of vascular cells, is essential for long-distance water conduction and structural support of plants. Independently of the species, each different vascular cell type contains a conserved lignin chemistry with specific aromatic and aliphatic substitutions. Yet, the biological role of this conserved and specific lignin chemistry for each cell type remained unclear. Herein, we investigate the role of specific lignin chemistries for cellular function by producing single cell analyses on vascular cell morphotypes, all enabling sap conduction but differing in morphology. We found that specific lignin chemistries accumulate in each morphotype. Moreover, lignin accumulates dynamically, increasing in quantity and changing composition, to alter the cell wall biomechanics of each morphotype during their maturation. For similar aromatic substitution, residues with alcohol aliphatic functions increased stiffness whereas aldehydes increased flexibility. Modifying this specific lignin chemistry impairs the cell wall biomechanics of each morphotype and consequently reduces their capacity to optimally conduct water in normal conditions, and to recover from drought. Altogether, lignin chemistry is differently controlled for each sap conducting cell types during their maturation to dynamically adjust their biomechanics and hydraulic properties to adapt to developmental and environmental constraints.

plant biology↗

bioRxiv2021

P. falciparum K13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites

The emergence of artemisinin (ART) resistance in Plasmodium falciparum parasites, driven by K13 mutations, has led to widespread antimalarial treatment failure in Southeast Asia. In Africa, our genotyping of 3,299 isolates confirms the emergence of the K13 R561H variant in Rwanda and reveals the continuing dominance of wild-type K13 across 11 countries. We show that this mutation, along with M579I and C580Y, confers varying degrees of in vitro ART resistance in African parasites. C580Y and M579I cause substantial fitness costs, which may counter-select against their dissemination in high-transmission settings. We also define the impact of multiple K13 mutations on ART resistance and fitness in multiple Southeast Asian strains. ART susceptibility is unaltered upon editing point mutations in ferrodoxin or mdr2, earlier resistance markers. These data point to the lack of an evident biological barrier to mutant K13 mediating ART resistance in Africa, while identifying their detrimental impact on parasite growth.

physiology↗

bioRxiv2021

Plasmodium falciparum K13 mutations in Africa and Asia present varying degrees of artemisinin resistance and an elevated fitness cost in African parasites

The emergence of artemisinin (ART) resistance in Plasmodium falciparum parasites has led to increasing rates of treatment failure with first-line ART-based combination therapies (ACTs) in Southeast Asia. In this region, select mutations in K13 can result in delayed parasite clearance rates in vivo and enhanced survival in the ring-stage survival assay (RSA) in vitro. Our genotyping of 3,299 P. falciparum isolates across 11 sub-Saharan countries reveals the continuing dominance of wild-type K13 and confirms the emergence of a K13 R561H variant in Rwanda. Using gene editing, we provide definitive evidence that this mutation, along with M579I and C580Y, can confer variable degrees of in vitro ART resistance in African P. falciparum strains. C580Y and M579I were both associated with substantial fitness costs in African parasites, which may counter-select against their dissemination in high-transmission settings. We also report the impact of multiple K13 mutations, including the predominant variant C580Y, on RSA survival rates and fitness in multiple Southeast Asian strains. No change in ART susceptibility was observed upon editing point mutations in ferrodoxin or mdr2, earlier associated with ART resistance in Southeast Asia. These data point to the lack of an evident biological barrier to mutant K13 mediating ART resistance in Africa, while identifying their detrimental impact on parasite growth.

microbiology↗

bioRxiv2020

Real time, field-deployable whole genome sequencing of malaria parasites using nanopore technology

Malaria parasite genomes have been generated predominantly using short read sequencing technology which can be slow, requires advanced laboratory training and does not adequately interrogate complex genomic regions that harbour important malaria virulence determinants. The portable Oxford Nanopore Technologies MinION platform generates long reads in real time and may overcome these limitations. We present compelling evidence that Nanopore sequencing delivers valuable additional information for malaria parasites with comparable data fidelity for single nucleotide variant (SNV) calls, compared to standard Illumina whole genome sequencing. We demonstrate this through sequencing of pure Plasmodium falciparum DNA, mock infections and natural isolates. Nanopore has low error rates for haploid SNV genotyping and identifies structural variants (SVs) not detected with short reads. Nanopore genomes are directly comparable to publically available genomes and produce high quality end to end chromosome assemblies. Nanopore sequencing will expedite genomic surveillance of malaria and provide new insights into parasite genome biology.

genomics↗

bioRxiv2018

High proportion of multiple copies of Plasmodium falciparum Plasmepsin-2 gene in African isolates: Is piperaquine resistance emerging in Africa?

Emergence of Plasmodium falciparum resistance to antimalarial drugs is currently the primary rationale supporting the development of new and well-tolerated drugs. In 2014-2015, a phase 2b clinical study was conducted to evaluate the efficacy of a single oral dose of Artefenomel (OZ439)-piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria. Blood samples collected before treatment offered the opportunity to investigate the proportion of multidrug resistant parasite genotypes including P. falciparum Kelch13 mutations and copy number variation of both P. falciparum plasmepsin2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes. Validated Kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated to PPQ resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (>30%).\n\nOur findings sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to decipher the genetic background associated with PPQ resistance in Africa by investigating in vitro susceptibilities to PPQ of isolates with multiple copies of the Pfpm2 gene and the urgent need to assess the risk of development of PPQ resistance, along with the efficacy of both current frontline therapies and new antimalarial combinations.

microbiology↗

bioRxiv2018

In vivo gene expression analyses provide unique insights on P. vivax gametocytogenesis and chloroquine response

Studies of gene expression have provided insights on the regulation of Plasmodium parasites. However, few studies have targeted P. vivax, the cause of one third of all human malaria cases outside Africa, due to the lack of in vitro culture system and the difficulties associated with studying clinical samples. Here, we describe robust RNA-seq profiles of P. vivax parasites generated directly from infected patient blood. Gene expression deconvolution analysis reveals that most parasite mRNAs derive from trophozoites and that the asynchronicity of P. vivax infections is unlikely to confound gene expression studies. We also show that gametocyte genes form two clusters of co-regulated genes, possibly indicating the independent regulation of male and female gametocytogeneses. Finally, despite a large effect on parasitemia, we find that chloroquine does not alter trophozoite gene expression. Overall, our study highlights the biological knowledge that can be gathered by directly studying P. vivax patient infections.\n\nImportancePlasmodium vivax is the second most common cause of human malaria worldwide but, since it cannot be cultured in the laboratory, its biology remains poorly understood. In this study, we describe the analysis of the parasite gene expression profiles generated from 26 patient infections. We show that the proportion of male and female parasites varies greatly among infections, suggesting that they are independently regulated. We also compare the gene expression profiles of the same infections before and after treatment with chloroquine, a common antimalarial, and show that the drug efficiently kills most P. vivax parasites but appears to have little effect on one specific parasite stage, the trophozoites, in contrast with the effect of the drug on P. falciparum. Overall, our study exemplifies the biological insights that can be gained from applying modern genomic tools to study this difficult human pathogen.

microbiology↗

bioRxiv2018

Genetic diversity in two Plasmodium vivax protein ligands for reticulocyte invasion

The interaction between Plasmodium vivax Duffy binding protein (PvDBP) and Duffy antigen receptor for chemokines (DARC) has been described as critical for the invasion of human reticulocytes, although increasing reports of P. vivax infections in Duffy-negative individuals questions its unique role. To investigate the genetic diversity of the two main protein ligands for reticulocyte invasion, PvDBP and P. vivax Erythrocyte Binding Protein (PvEBP), we analyzed 458 isolates collected in Cambodia and Madagascar. First, we observed a high proportion of isolates with multiple copies PvEBP from Madagascar (56%) where Duffy negative and positive individuals coexist compared to Cambodia (19%) where Duffy-negative population is virtually absent. Whether the gene amplification observed is responsible for alternate invasion pathways remains to be tested. Second, we found that the PvEBP gene was less diverse than PvDBP gene (12 vs. 33 alleles) but provided evidence for an excess of nonsynonymous mutations with the complete absence of synonymous mutations. This finding reveals that PvEBP is under strong diversifying selection, and confirms the importance of this protein ligand in the invasion process of the human reticulocytes and as a target of acquired immunity. These observations highlight how genomic changes in parasite ligands improve the fitness of P. vivax isolates in the face of immune pressure and receptor polymorphisms.

genetics↗