Biology subjects

Pascal, M.

Publications and source records attributed to Pascal, M..

6 recordsLinked to original sources

bioRxiv2025

Pyrethroid resistance intensity in Anopheles gambiae s.l. mosquito populations from Rwanda

Evidence based vector control interventions depends on understanding the distribution and the evolution of insecticide resistance in malaria vectors. This study aims to assess the status of insecticide resistances in Anopheles gambiae s.l., to pyrethroid insecticides such as permethrin, deltamethrin and alphacypermethrin from 18 study sites located in 15 districts across Rwanda, representing the key strata of malaria transmission in country. The larvae of anopheles were collected from October 2022 to April 2023 using dipping method, and reared to adult stage. The An. gambiae were exposed to alphacypermethrin 0.05% (Acyp_1X), permethrin 0.75% (Perm_1X), and deltamethrin 0.05% (Delth_1X) then tested using WHO bioassay standard protocol for insecticide resistance monitoring. As results, we found an extremely high resistance to permethrin in Gashora (Bugesera district), Mubuga (Karongi district), Rwaza (Musanze district), Kirarambogo (Gisagara district) with mortality rate of 42%, 48%, 69% and 70% repsectively. Subsquently, no recovery of susceptibility was observed in permethrin after pre-exposure to piperonyl butoxide (PBO) and observed mortality was 70% in Kirarambogo, while in Gashora, Mubuga and Rwanza it was 80% at each site. In city of Kigali, the mortality with alphacypermethrin was 94% and 93% with synergist PBO. Notably, in Kicukiro district we found that metabolic resistance mechanism was not driving the resistance mechanisms. These findings provide important understandings of pyrethroid resistance status in Rwanda and offering valuable insights for distribution of insecticide resistance intensity across country. This highlights the need for further studies to assess the spread of insecticide resistance and molecular driven resistance mechanism to address the issue in malaria vector control in Rwanda.

evolutionary biology↗

bioRxiv2024

mRNA-delivered consensus allergens induce a neutralizing IgG response against food and pollen allergens

Pollen-food allergy syndrome (PFAS) affects a significant proportion of the global population with a major health and socioeconomic impact. Patients are generally treated against the major sensitized allergen which does not warrant protection against cross-reactive allergens, leading to long and ineffective treatment regimens. For food allergies, patient guidelines rely on source avoidance, leading to dietary restrictions and reduced quality of life - in particular for those suffering from PFAS. To overcome these limitations, we introduce a novel allergy immunotherapy (AIT) approach utilizing consensus allergens and mRNA technology to achieve broader, safer, and faster desensitization in PFAS patients. We first designed a consensus allergen of orthologs of non-specific Lipid Transfer Proteins (cnsLTP-1) representing a broad spectrum of nsLTP allergens prevalent in food and pollen sources. CnsLTP-1 was delivered to naive BALB/c mice using mRNA-lipid nanoparticles (mRNA-LNP) as vehicle, or by a traditional protein formulation, to assess if it elicits broad protection against allergens from different sources. Immunization with both mRNA-LNP and protein formulations demonstrated that cnsLTP-1-specific IgGs could be induced, whilst the mRNA-LNP formulation notably avoided the induction of allergen-specific IgEs. The induced antibodies were capable of recognizing and binding to a variety of nsLTPs, and effectively blocked the binding of allergens by allergic patient serum IgEs. This study thus demonstrates that the presented AIT strategy, based on mRNA-LNP technology and consensus allergens, could find clinical utility by addressing the limitations of current AIT. Further development of this technology platform could pave the way for more effective and patient-friendly treatments for PFAS and other cross-reactive allergies.

bioengineering↗

bioRxiv2023

Integration of QTL and transcriptome approaches for the identification of genes involved in tomato response to nitrogen deficiency

Optimising plant nitrogen (N) usage and inhibiting N leaching loss in the soil-crop system is crucial to maintain crop yield and reduce environmental pollution. This study aimed at identifying quantitative trait loci (QTL) and differential expressed genes (DEGs) between two N treatments in order to list candidate genes related to nitrogen-related contrasting traits in tomato varieties. We characterised a genetic diversity core-collection (CC) and a multi-parental advanced generation intercross (MAGIC) tomato population grown in greenhouse under two nitrogen levels and assessed several N-related traits and mapped QTLs. Transcriptome response under the two N conditions was also investigated through RNA sequencing of fruit and leaves in four parents of the MAGIC population. Significant differences in response to N input reduction were observed at the phenotypic level for biomass and N-related traits. Twenty-seven (27) QTLs were detected for three target traits (Leaf N content, leaf Nitrogen Balance Index and petiole NO3- content), ten and six at low and high N condition, respectively; while 19 QTLs were identified for plasticity traits. At the transcriptome level, 4,752 and 2,405 DEGs were detected between the two N conditions in leaves and fruits, respectively, among which 3,628 (50.6%) in leaves and 1,717 (71.4%) in fruit were genotype specific. When considering all the genotypes, 1,677 DEGs were shared between organs or tissues. Finally, we integrated DEGs and QTLs analyses to identify the most promising candidate genes. The results highlighted a complex genetic architecture of N homeostasis in tomato and novel putative genes useful for breeding improved-NUE tomato. HighlightTomato response to nitrogen deficiency is genetically controlled by a few QTLs and impacts the expression of a large number of genes, among which some are good targets for breeding sober varieties.

plant biology↗

bioRxiv2023

Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

The human nasopharyngeal mucosa includes organized lymphoepithelial structures continually engaged in frontline immune responses to aerodigestive antigens. Advancing our understanding of these responses might lead to the development of new strategies for the prevention and treatment of common immune disorders such as allergies. Here we identified a hitherto elusive tonsillar subset of atypical IgD class-switched IgD+IgM- memory (IgD-ME) B cells that were clonally related to IgD+IgM- germinal center (IgD-GC) B cells and IgD-secreting IgD+IgM- plasma cells (IgD-PCs) but not anergic IgD+IgM- B cells. Consistent with their pre-plasmacellular properties, IgD-ME B cells served as preferential precursors of IgD-PCs over IgD-GC B cells. IgD antibodies from IgD+IgM- cells acquired reactivity to multiple oral, airborne and commensal antigens through a mutation-dependent pathway involving both innate and adaptive signals. Thus, IgD-ME B cells may form a ready-to-use pre-plasmacellular reservoir for steady-state IgD responses likely aimed at enhancing nasopharyngeal homeostasis. One Sentence SummaryTonsillar atypical memory B cells form a ready-to-use pre-plasmacellular repertoire for IgD responses to common aerodigestive antigens.

immunology↗

bioRxiv2019

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations -- characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors -- which could be transferred from UCMS donors to naive recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota on adult neurogenesis and behavior in naive recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

neuroscience↗

bioRxiv2019

Optimization and validation of a quadruplex real-time PCR assay for the diagnosis of diphtheria

Diphtheria is caused by toxigenic strains of Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis. For diagnostic purposes, species identification and detection of toxigenic strains (diphtheria toxin (tox)-positive strains) is typically performed using end-point PCR. A faster quadruplex real-time PCR (qPCR) was recently developed (De Zoysa et al. J Med Microbiol. 2016 65(12):1521-1527). Here, we present an improvement of the quadruplex method, in which a 16S rRNA gene target was added as an internal processing control, providing confirmation of the presence of bacterial DNA in the assays. This improved qPCR method was validated using 36 bacterial isolates and 16 clinical samples. The method allows detection of the tox gene and distinguishing C. diphtheriae (including the newly described species C. belfantii) from C. ulcerans and C. pseudotuberculosis. Complete diagnostic specificity, sensitivity and experimental robustness of the method to temperature and reagent concentration variations were demonstrated. The lower limit of detection for C. diphtheriae, C. ulcerans and tox targets was 1.86 genome copies per 5 L reaction volume. Finally, the method was successfully used on two distinct qPCR technologies (LightCycler 480, Roche Diagnostics and Rotor-Gene Q, Qiagen) and in two laboratories (Institut Pasteur, Paris, France and Public Health England - National Infection Service, London, UK). This work describes validation of the improved qPCR quadruplex method and supports its implementation for the biological diagnosis of diphtheria.

microbiology↗