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Renaud, F.

Publications and source records attributed to Renaud, F..

7 recordsLinked to original sources

Transforming Esogastric Cancer Surgery Integrating SpiderMass Mass Spectrometry with Clinical and Microbiome Data for Margin Delineation and Prognosis

Esophageal-gastric cancers (EC) represent a significant global health concern, with esophageal cancer ranking seventh in terms of incidence and mortality worldwide. Gastric cancer is especially concerning, with an estimated one million new cases and 800,000 deaths annually. Late diagnoses often lead to poor outcomes, requiring critical interventions such as radical surgical resection with clear margins, in conjunction with chemotherapy, or radiotherapy to prevent recurrences and enhance survival. Thus, EC represents a significant clinical challenge, especially given the difficulty in achieving precise surgical margins in aggressive subtypes like poorly cohesive carcinoma (PCC). Moreover, pathological intraoperative margin assessment encounters significant issues, especially for PCCs, due to lacks of sensitivity for microscopic infiltration, potentially leading to recurrence and poorer patient outcomes. We address these critical limitations by integrating SpiderMass, an ambient mass spectrometry (MS) technology, with clinical metadata and microbiome profiling couple along with Machine learning. We demonstrate SpiderMass capability in real-time molecular margin delineation and identify distinct lipidomic and microbiome signatures correlating with tissue type and prognosis. Our integrative approach provides a more precise and biologically informative intraoperative diagnostic tool, significantly enhancing surgical decision-makin, to improve patient outcomes and extend survival.

cancer biology↗

Population genomic evidence of a Southeast Asian origin of Plasmodium vivax

Plasmodium vivax is the most prevalent and widespread human malaria parasite, with almost three billion people living at risk of infection. With the discovery of its closest genetic relatives in African great apes (Plasmodium vivax-like), the origin of P. vivax has been proposed to be located in the sub-Saharan African area. However, the limited number of genetic markers and samples investigated questioned the robustness of this result. Here, we examined the population genomic variation of 447 human P. vivax strains and 19 ape P. vivax-like strains originating from 24 different countries across the world. We identified 2,005,455 high quality single-nucleotide polymorphism loci allowing us to conduct an extensive characterization to date of P. vivax worldwide genetic variation. Phylogenetic relationships between human and ape Plasmodium revealed that P. vivax is a sister clade of P. vivax-like, not included within the radiation of P. vivax-like. By investigating a variety of aspects of P. vivax variation, we identified several striking geographical patterns in summary statistics as function of increasing geographic distance from Southeast Asia, suggesting that P. vivax may derived from serial founder effects from a single origin located in Asia.

evolutionary biology↗

Infection triggers tumor regression through activation of innate immunity in Drosophila

The pioneering work of Dr. William Coley has shown that infections can stimulate the immune system and improve tumor growth control. However, the immune mechanisms responsible for the protective role of infectious agents have still not been identified. Here, we investigated the role of innate immune pathways in tumor regression by performing experimental infections in genetically modified Drosophila that develop invasive neoplastic tumors. After quantifying tumor size, through image processing, and immune gene expression with transcriptomic analyses, we analyzed the link between tumor size and pathogen-induced immune responses thanks to a combination of statistical and mathematical modeling. Drosophila larvae infected with a naturally-occurring bacterium showed a smaller tumor size compared to controls and fungus-infected larvae, thanks to an increase expression of Imd and Toll pathways. Our mathematical model reinforces this idea by showing that repeated acute infection could results in an even higher decrease in tumor size. Thus, our study suggests that infectious agents can induce tumor regression through the alteration of innate immune responses. This phenomenon, currently neglected in oncology, could have major implications for the elaboration of new preventive and immunotherapeutic strategies. One Sentence SummaryBacterial infections can decrease cancer cell accumulation through stimulation of innate immune responses.

immunology↗

Field evidence for manipulation of mosquito host selection by the human malaria parasite, Plasmodium falciparum

Whether the malaria parasite Plasmodium falciparum can manipulate mosquito host choice in ways that enhance parasite transmission toward humans is unknown. We assessed the influence of P. falciparum on the blood-feeding behaviour of three of its major vectors (Anopheles coluzzii, An. gambiae and An. arabiensis) in Burkina Faso. Host preference assays using odour-baited traps revealed no effect of infection on mosquito long-range anthropophily. However, the identification of the blood meal origin of mosquitoes showed that females carrying sporozoites, the mature transmissible stage of the parasite, displayed a 24% increase in anthropophagy compared to both females harbouring oocysts, the parasite immature stage, and uninfected individuals. Using a mathematical model, we further showed that this increased anthropophagy in infectious females resulted in a > 250% increase in parasite transmission potential, everything else being equal. This important epidemiological consequence highlights the importance of vector control tools targeting infectious females.

evolutionary biology↗

Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution

Plasmodium vivax is responsible of the majority of malaria infections outside Africa. Its closer genetic relative, Plasmodium vivax-like, was discovered in African great apes and suggested to have given rise to P. vivax in humans. We generated two newly P. vivax-like reference genomes and 9 additional P. vivax-like genotypes, to unravel the evolutionary history of P. vivax. We showed a clear separation between the two clades, a higher genetic diversity of P. vivax-like parasites in comparison to the P. vivax ones, and the potential existence of two sub-clades of P. vivax-like. We dated the relative split between P. vivax and P. vivax-like as three times shorter than the split between P. ovale wallikeri and P. ovale curtesi and 1.5 times longer than the split between Plasmodium malariae. The sequencing of the P. vivax-like genomes is an undeniable advance in the understanding of P. vivax biology, evolution and emergence in human populations.

evolutionary biology↗

Can malaria parasites manipulate the odour-mediated host preference of their mosquito vectors?

Malaria parasites can manipulate mosquito feeding behaviours such as motivation and avidity to feed on vertebrate hosts in ways that increase parasite transmission. However, in natural conditions, not all vertebrate blood-sources are suitable hosts for the parasite. Whether malaria parasites can manipulate mosquito host choice in ways that enhance parasite transmission toward suitable hosts and/or reduce mosquito attraction to unsuitable hosts (i.e. specific manipulation) is unknown. To address this question, we experimentally infected three species of mosquito vectors (Anopheles coluzzii, Anopheles gambiae, and Anopheles arabiensis) with wild isolates of the human malaria parasite Plasmodium falciparum, and examined the effects of immature (oocyst) and mature (sporozoite) infections on mosquito behavioural responses (activation rate and odour choice) to combinations of calf odour, human odour and outdoor air using a dual-port olfactometer. Regardless of parasite developmental stage and mosquito species, P. falciparum infection did not alter mosquito activation rate or their choice for human odours. The overall expression pattern of host choice of all three mosquito species was consistent with a high degree of anthropophily, with both infected and uninfected individuals showing higher attraction toward human odour over calf odour, human odour over outdoor air, and outdoor air over calf odour. Our results suggests that, in this system, the parasite may not be able to manipulate the early long-range behavioural steps involved in the mosquito host-feeding process, including initiation of host-seeking and host orientation. Future studies examining mosquito host-feeding behaviours at a shorter range (i.e. the \"at-host\" foraging activities) are required to test whether malaria parasites can modify their mosquito host choice to enhance transmission toward suitable hosts and/or reduce biting on unsuitable hosts.

evolutionary biology↗

Genomes of an entire Plasmodium subgenus reveal paths to virulent human malaria

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum. Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor shows a host specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate confidently for the first time the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.

evolutionary biology↗