Biology subjects

Duval, D.

Publications and source records attributed to Duval, D..

5 recordsLinked to original sources

bioRxiv2025

Comparative multi-omics analysis uncovers contrasting molecular profiles of canine and human thyroid carcinomas

Thyroid tumors represent 1-3% of canine cancers, with most tumors classified as follicular carcinomas and less frequently as medullary carcinomas. In comparison, only 10-15% of human thyroid cancers are follicular and 2% are medullary, with prevalent activating mutations in BRAF and NRAS, or RET, respectively. A cohort of canine thyroid carcinomas underwent histopathological (n=60 and paired molecular (n=30, WES and/or RNAseq) exploration. Clustering of tumor transcriptomes produced 2 groups; T1 and T2 clusters comprised of follicular thyroid carcinomas (FTC) and medullary thyroid carcinomas (MTC), respectively. Tumors were histologically typed as follicular, compact, and follicular-compact on blinded review, with most MTC classified as compact with rare follicular-compact appearance, while FTC displayed all 3 patterns. FTC samples had significantly elevated levels of ERBB2 and HER2 protein, and RET signaling was up-regulated in MTC. Recurrent somatic mutations in DNMT1, STAT2, SALL4, HSP90AA1, MEN1, MUC4, THRAP3, CDK4, NOTCH2, and THRAP3 were identified in at least 10% of samples. Individual variants were also identified in KRAS, ARAF, GNAS, and ERBB2. Additionally, we identified fusion genes that included TG, FGFR2, and PAX8. These data suggest that canine MTC, like their human counterparts, may be driven by RET signaling. In contrast, FTC show limited reliance on RAS/RAF signaling, prevalent in human TC, for oncogenic progression. Across the analyzed samples, 60% of tumors had mutations in at least one DNA repair-related pathway, suggesting that the accumulation of DNA damage may drive cancer progression in canine thyroid tumors. Elevated HER2 protein staining was associated with shorter progression free survival (PFS). Thyroid tumor size (>4.25 cm) was also associated with shorter overall survival and PFS, consistent with previous reports; however, metastasis at diagnosis was not correlated with outcome. Additional studies are warranted to explore the utility of these biomarkers to improve diagnosis and treatment of thyroid carcinoma in dogs.

cancer biology↗

bioRxiv2019

Chromatin structure changes in Daphnia populations upon exposure to environmental cues - or - The discovery of Wolterecks \"Matrix\"

Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20th century by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as \"norm of reaction\". Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-flee daphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called the Matrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Wolterecks classical experiments with daphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Wolterecks classical postulate.

evolutionary biology↗

bioRxiv2018

Dysbiosis of the Biomphalaria glabrata vector snail microbiota following infection by Schistosoma parasites

Host-associated microbiota cari affect the fitness of its host i {eta} a number of ways, including the modification of host-parasite interactions and thus the outcome of disease. Biomphalaria glabrata is the vector snail of the trematode Schistosoma mansoni, the agent of human schistosomiasis, causing hundreds of thousands of deaths every year. Here, we present the first study of the snail bacterial microbiota in response to Schistosoma infection. To examine the interplay between B. glabrata, S. mansoni and snail microbiota, snails were infected and the microbiota composition was analysed by massive 16S rDNA amplicon sequencing approach. We characterized the Biomphalaria bacterial microbiota at the individual level in both naive and infected snails. Sympatric and allopatric strains of parasites were used for infections and re{-}infections to analyse the modification or dysbiosis of snail microbiota in different host-parasite co-evolutionary contexts. Concomitantly, using RNAseq data, we investigated the link between bacterial microbiota dysbiosis and snail anti-microbial peptide immune response. This work paves the way for a better understanding of snail/schistosome interaction, and would have critical consequences in terms of snail control strategies for fighting schistosomiasis disease in the field.

microbiology↗

bioRxiv2018

Sympatric and allopatric evolutionary contexts shape differential immune response in Biomphalaria / Schistosoma interaction

Selective pressures between hosts and their parasites can result in reciprocal evolution or adaptation of specific life history traits. Local adaptation of resident hosts and parasites should lead to host-parasite systems performing better in sympatry when compared to allopatry. Between-population variations in parasite infectivity/virulence and host defence/resistance, referred to as compatibility phenotype, were often the proxy used to analyse sympatric or allopatric adaptation. Nevertheless, some reported cases exist where allopatric host-parasite systems demonstrate compatibility phenotypes similar or greater than the one observed in sympatry. In these cases, the role of local adaptation is worth considering. Here, we study the interaction between Schistosoma and its vector snail Biomphalaria in which such a discrepancy in local versus foreign compatibility phenotype has been observed. Herein, we developed an integrative approach to investigate sympatric and allopatric interaction processes and link the underlying molecular mechanisms to the resulting phenotypes. Using comparative \"omics\" approaches joined to analysis of life history traits (immune cellular response, mortality, prevalence and compatibility) we tried to bridge the gap of knowledge that exists for connecting local adaptation observations to molecular phenotypes in Schistosoma/Biomphalaria interactions.\n\nWe found that despite displaying similar prevalence phenotypes, parasite infection triggered an immune suppression in snails living in sympatry, while it activated an immune response for those living in allopatry. Dual-comparative molecular analyses revealed that parasite infection causes immune suppression in sympatry. miRNAs were used to hijack the hosts immune response, allowing sympatric parasites to initiate their developmental program earlier and more efficiently.\n\nWe show that despite having similar prevalence phenotypes, sympatric and allopatric snail-Schistosoma interactions displayed a strongly different immunobiological molecular dialogue. The ability of allopatric pathogens to adapt rapidly and efficiently to new hosts could have critical consequences on disease emergence and risk of schistosomiasis outbreaks. These observations would have important consequences in term of schistosomiasis disease control.

immunology↗

bioRxiv2018

BgTEP: an antiprotease involved in innate immune sensing in Biomphalaria glabrata

Insect Thioester-containing protein (iTEP) is the most recently defined group among the TEP superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterised from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians and mollusks albeit with few functional characterisations. In the freshwater snail Biomphalaria glabrata, a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (FREP) and schistosome parasite mucins (SmPoMuc).\n\nTo investigate the potential role of BgTEP in the immune response of the snail, we first characterised its genomic organisation and its predicted protein structure. A phylogenetic analysis clustered BgTEP in a well-conserved subgroup of mollusk TEP. We then investigated the BgTEP expression profile in different snail tissues, and followed immune challenges using different kinds of intruders during infection kinetics. Results revealed that BgTEP is particularly expressed in hemocytes, the immune-specialised cells in invertebrates, and is secreted into the hemolymph. Transcriptomic results further evidenced an intruder-dependent differential expression pattern of BgTEP whilst interactome experiments showed that BgTEP is capable of binding to the surface of different microbes and parasite either in its full length form or in processed forms.\n\nThrough this work, we report the first characterisation of a snail TEP. Our study also reveals that BgTEP may display an unexpected functional dual-role. In addition to its previously characterised anti-protease activity, we demonstrate that BgTEP can bind to the intruder surface membrane, which supports a likely opsonin role.

immunology↗