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Desjardins, A.

Publications and source records attributed to Desjardins, A..

5 recordsLinked to original sources

First nationwide mosquito surveillance in Northern Irish wetlands reveals presence of Culex pipiens/molestus hybrids

While mosquito invasions and associated pathogens are increasingly prominent in Europe, evidence gaps remain for many northerly regions where proactive management interventions may be most effective. At the regional periphery of Europe, there remains a significant knowledge gap concerning mosquito vector distributions in Northern Ireland. This study aimed to address this major gap by systematically surveying larval and adult mosquito populations in key habitats (ponds, reedbeds, saltmarsh, wet grasslands, wet woodlands, and urban gardens). We further identified environmental drivers of important vector species abundance and screened collected specimens with molecular techniques to identify presence of cryptic human-biting vector species. In Northern Ireland, mosquitoes (including potential bridge vectors of West Nile and Usutu viruses) were found to be widely distributed. Between May and August 2025, a total of 2430 mosquitoes (951 adults and 1479 larvae) were collected over 196 trap nights and 76 larval collections. Collections encompassed 17 species, with Culex pipiens/torrentium being the most widely distributed and abundant taxon recorded. Mosquito abundances were greatest in reedbed habitats, related negatively with rainfall and peaked in June and July. A subset of Culex pipiens/torrentium mosquitoes were identified to species/biotype level using PCR, with the majority (89.3%) identified as Culex pipiens pipiens and 9.3% as Culex torrentium. Importantly, the first detections of Culex pipiens/molestus hybrids (1.8%) on the island of Ireland were found. This work underscores the wide, yet previously undocumented abundance and distribution of potential zoonotic vectors in Northern Ireland and provides an important baseline for management planning and future research, while contributing to broader understandings of environmental population drivers and distributions.

ecology↗

Multi-Omics Study of Ancestry in Adults with Intracranial Cancers Glioma (MOSAIC)

BackgroundMost genomic studies of adult-type diffuse gliomas have focused on predominantly European ancestry populations, limiting the generalizability of molecular classifications and precision medicine approaches. We assembled a multi-institutional glioma cohort of diverse patients to investigate how germline ancestry, molecular subtypes, and mutational processes shape tumor biology and clinical outcomes. MethodsWe analyzed 1,102 adults with WHO 2021-classified diffuse gliomas (IDH-mutant, 1p/19q-codeleted oligodendroglioma; IDH-mutant astrocytoma; IDH-wildtype glioma) from seven U.S. institutions. Whole-exome sequencing (WES) of FFPE tumors identified somatic alterations and COSMIC SBS v3.2 mutational signatures. Genetic ancestry was estimated from WES using 1000 Genomes reference populations. Overall survival was assessed using Kaplan-Meier and multivariable models. ResultsThe cohort included 66.9% European (EUR), 21.1% Admixed American/Hispanic (AMR), 10.3% Admixed African (AFR), and 1.6% Asian (AS) ancestry. Survival followed expected molecular hierarchy (median overall survival: oligodendroglioma 15.7 years, astrocytoma 10.6 years, IDH-wildtype glioma 1.9 years). Within oligodendroglioma, AMR patients showed improved survival versus EUR (HR 0.67, 95% CI 0.48-0.94; p=0.011), with similar trends across subtypes. Somatic profiling confirmed canonical subtype-defining alterations and revealed higher ATRX alterations in AFR and AMR IDH-wildtype tumors compared with EUR. ATRX alterations were associated with improved survival only in AFR (p=0.003). Mutational signature analysis identified subtype-specific signatures, including therapy-associated signatures. Chemotherapy-related signatures were more frequent in EUR and AMR than in AFR. ConclusionsThis ancestrally diverse glioma cohort confirms established molecular classifications and identifies ancestry-associated differences in survival, somatic alterations, and mutational processes, indicating the critical need for broad representation to inform precision neuro-oncology. Key PointsO_LIA multi-institutional glioma cohort validates subtype and survival patterns across ancestries. C_LIO_LITherapy-associated mutational signatures differ by ancestry, suggesting distinct treatment-related mutational processes. C_LIO_LIAdmixed American patients show improved survival, particularly in oligodendroglioma. C_LI Importance of the StudyMost genomic studies of adult-type diffuse glioma have focused on populations of predominantly European ancestry which limits the ability to examine variation in tumor biology and clinical outcomes across populations. In this study, we assembled one of the largest ancestrally diverse cohorts of molecularly characterized adult diffuse gliomas, integrating germline ancestry inference with tumor whole-exome sequencing and mutational signature analysis. We confirm that established molecular classifications and survival hierarchies remain robust across ancestry groups. However, we also identified ancestry-associated differences in survival within specific tumor subtypes, higher ATRX alteration frequencies in African American and admixed American patients with IDH-wildtype tumors, and variation in therapy-associated mutational signatures across ancestry groups. These findings highlight the importance of incorporating population differences into genomic studies of glioma and provide a resource for future multi-ancestry investigations of glioma risk, tumor evolution, and treatment response, ultimately supporting more inclusive precision neuro-oncology.

bioinformatics↗

Microbiota-derived extracellular vesicles link intestinal dysbiosis to neuroimmune activation in long COVID

Post COVID-19 condition (Long COVID, LC) is frequently accompanied by persistent neurological symptoms, but the mechanisms linking intestinal dysbiosis to neuroinflammation remain unclear. Here we identify gut microbiota-derived extracellular vesicles (GMEVs) as functional mediators linking LC-associated dysbiosis to systemic and neuroimmune inflammation. In a longitudinally characterized cohort, individuals with LC and neurological symptoms exhibit a persistent intestinal microbiome signature. Transplantation of LC-associated microbiota into germ-free mice induces intestinal barrier disruption and neuroinflammatory phenotypes. GMEVs from individuals with LC activate inflammasome-associated programs and impair epithelial barrier function, promote inflammatory responses in macrophages, and induce coordinated pro-inflammatory transcriptional programs in human induced pluripotent stem cell (iPSC)-derived microglia. Chronic oral administration of LC-derived GMEVs remodels the microbiota and induces intestinal and systemic inflammation with glial activation in vivo. Together, these findings support a vesicle-centered framework in which microbiota-derived extracellular vesicles translate dysbiosis into sustained immune and neuroimmune activation in a post-viral inflammatory state.

microbiology↗

A microRNA CRISPR screen reveals miR-483-3p as an apoptotic regulator in prostate cancer

The development of traditional protein-targeted cancer therapies is a slow and arduous process, often taking years or even decades. In contrast, RNA-based therapies targeting crucial microRNAs (miRNAs) offer a faster alternative due to the sequence specific nature of miRNA inhibitor binding. This, combined with the capacity of individual miRNAs to influence multiple cellular pathways, makes these small RNAs attractive targets for cancer therapy. While miRNA are known to be dysregulated in prostate cancer (PCa), identifying their individual contributions to disease progression and the identification of therapeutically actionable miRNA targets in PCa has been challenging due to limited screening tools. To overcome this, we developed miRKOv2, a miRNA-only CRISPR knockout library enabling systematic, genome-wide loss-of-function screens to identify miRNAs essential for PCa cell survival. Our screens uncovered 69 potential essential miRNA candidates, with miR-483 demonstrating the most significant impact on PCa cell viability. Functional characterization demonstrated that miR-483 disruption significantly potentiated apoptosis in PCa cell lines. Mechanistically, we uncovered a novel regulatory axis wherein miR-483-3p directly modulates a BCLAF1/PUMA/BAK1 apoptotic signaling network, highlighting its critical role in maintaining PCa cell survival. Our findings provide novel insights into the complex regulatory role of miRNA in PCa progression and offer a potential therapeutic strategy for targeting miRNA-mediated pathways in metastatic disease.

cancer biology↗

Combining optical imaging of cleared tissue with mathematical modelling to predict drug delivery and therapeutic response

Understanding how drugs are delivered to diseased tissue, and their subsequent spatial and temporal distribution, is a key factor in the development of effective, targeted therapies. However, the interaction between the pathophysiology of diseased tissue and individual therapeutic agents can be complex, and can vary significantly between individuals. In cancer, suboptimal dosing resulting from poor delivery can cause reduced treatment efficacy, upregulation of resistance mechanisms and can even stimulate growth. Preclinical tools to better understand drug delivery are therefore urgently required, which incorporate the inherent variability and heterogeneity of human disease. To meet this need, we have combined multiscale mathematical modelling, high-resolution optical imaging of intact, optically-cleared tumour tissue from animal models, and in vivo magnetic resonance imaging (MRI). Our framework, named REANIMATE (REAlistic Numerical Image-based Modelling of biologicAl Tissue substratEs) allows large tissue samples to be investigated as if it were a living sample, in detailed, highly controlled, computational experiments. Specifically, we show that REANIMATE can be used to predict the heterogeneous delivery of specific therapeutic agents, in disparate two murine xenograft models of human colorectal carcinoma. Given the wide adoption of optical clearing equipment in biomedical research laboratories, REANIMATE enables a new paradigm in cancer drug development, which could also be applied to other disease areas.

biophysics↗