Le lac Léman à l’âge du Bronze: L’exemple du secteur du Petit Lac : les enjeux d’une dynamique de territoire

National audienceLake Geneva forms both a boundary and a natural passage. In the western part the area of the Small Lake hosts a large number of recent discoveries and makes it possible to carry out an analysis of the structural data of human settlements. An initial attempt to carry out an archaeogeographic study of the occupations according to possible road constructions and plots of land finally resulted in a heterogeneous set of data. However, this diversity of sites, their locations and their situations enabled us to carry out a different type of study by analysing the social space represented by each site compared to the other sites. However, this approach means questioning the type of object taken into account. The geographical peculiarity of the occupations leads to the creation of a graphic rendering that can take into account, inherently, each site as being a unit of a region or a territory, forming part of a complex semiological and iconological economy. Each is considered as being an isolated consistent whole. In each case we will try to understand the phenomena that underlay the very structure of the local landscape organisation. As the latter was subject to complex dynamics, both spatial and temporal, it is not a matter of analysing a linear progression but rather of analysing multiple processes that contributed to the structuring of the sites. It is therefore necessary to create a reading grid of the space to be mapped which makes it possible to highlight the interrelations between the different territorial components. As a result, these make it possible to reveal territorial dynamics that will be advanced as a hypothesis. The proposed geographical study involves the coexistence of several “metastable elements”, i.e. elements linked by their geographical and temporal closeness. In the course of time, each entity witnessed the appearance of new forms accompanying the disappearance of the ancient ones. This morphogenesis has structured the space which leads us to an analysis of the relationships between the sites defined by the ‘place’, the ‘space’ and the ‘boundary’. It is essential that each of these notions to be defined in order to understand the social geography of the Bronze Age populations. Lastly, the comparison of archaeological data with their spatialisation makes it possible to question the hierarchical aspect of the sites and the social and economic organisation of the area.Le lac Léman forme à la fois une frontière et un formidable couloir de circulation naturel. À l’ouest, le secteur du Petit Lac, avec ses nombreuses découvertes récentes, permet d’envisager une analyse des données structurelles d’installation humaines. Après une tentative initiale d’étude archéogéographique des occupations selon les constructions viaires et parcellaires envisageables., c’est finalement un ensemble hétérogène de données qui en ressort. Cependant, cette diversité des sites, leurs emplacements et leurs situations permet un autre type d’étude, celle de l’analyse de l’espace social que représente chaque site par rapport aux autres. Ce raisonnement nécessite cependant de s’interroger sur le type d’objet pris en compte. La particularité géographique des occupations conduit à créer un rendu graphique qui puisse prendre en compte, de façon consubstantielle, chaque site comme une unité d’un terroir ou d’un territoire, faisant partie d’une économie sémiologique et iconologique complexe. Chacun est considéré comme un ensemble cohérent isolé. On cherchera à en comprendre, pour chacun, les phénomènes qui constituent la structure même de l’organisation paysagère locale. Cette dernière étant placée dans une dynamique complexe, à la fois spatiale et chronologique, il ne s’agit pas d’analyser un déroulement linéaire mais les processus multiples qui ont contribué à la structuration des sites. Il faut ainsi élaborer une grille de lecture de l’espace à cartographier qui permet de livrer les interrelations entre les différentes composantes territoriales. En conséquence, au travers d’elles, c’est la dynamique territoriale qui sera placée comme postulat. L’étude géographique proposée est la mise en coexistence de plusieurs éléments « métastables », c’est à dire liés par leur proximité géographique et chronologique. Au cours du temps, chaque entité a vu l’apparition de formes nouvelles accompagnant la disparition des anciennes. Cette morphogénèse a structuré l’espace qui nous conduit à une analyse des relations entre les sites définies par le lieu, l’espace et la frontière. Chacune de ces notions est indispensable à définir pour comprendre la géographie sociale des populations de l’âge du Bronze. Pour finir, le rapprochement de données archéologiques avec leur spatialisation permet de s’interroger sur l’aspect hiérarchique des sites et sur l’organisation sociale et économique du secteur

An Oil-Based Adjuvant Improves Immune Responses Induced by Canine Adenovirus-Vectored Vaccine in Mice

There is a significant need for highly effective vaccines against emerging and common veterinary infectious diseases. Canine adenovirus type 2 (CAV2) vectors allow rapid development of multiple vaccines and have demonstrated their potential in animal models. In this study, we compared the immunogenicity of a non-replicating CAV2 vector encoding the rabies virus glycoprotein with and without MontanideTM ISA 201 VG, an oil-based adjuvant. All vaccinated mice rapidly achieved rabies seroconversion, which was associated with complete vaccine protection. The adjuvant increased rabies antibody titers without any significant effect on the anti-CAV2 serological responses. An RT2 Profiler™ PCR array was conducted to identify host antiviral genes modulated in the blood samples 24 h after vaccination. Functional analysis of differentially expressed genes revealed the up-regulation of the RIG-I, TLRs, NLRs, and IFNs signaling pathways. These results demonstrate that a water-in-oil-in-water adjuvant can shape the immune responses to an antigen encoded by an adenovirus, thereby enhancing the protection conferred by live recombinant vaccines. The characterization of early vaccine responses provides a better understanding of the mechanisms underlying the efficacy of CAV2-vectored vaccines

Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency

International audienceAIMS: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient’s uracil (U) plasma concentration is mandatory before fluoropyrimidines (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH(2) ) concentrations, since they are essential in reliable DPD deficiency testing. METHODS: U and UH(2) concentrations were collected from 14 hospital laboratories. Stability in whole blood and plasma after centrifugation, the type of anticoagulant and long-term plasma storage were evaluated. The variation induced by time and temperature was calculated and compared to an acceptability range of ± 20%. Inter-occasion variability (IOV) of U and UH(2) was assessed in 573 patients double sampled for DPD-deficiency testing. RESULTS: Storage of blood samples before centrifugation at room temperature (RT) should not exceed 1 h, whereas cold (+4°C) storage maintains U stable after 5 hours. For patients correctly double sampled, IOV of U reached 22.4% for U (SD = 17.9%, range = [0-99%]). Notably, 17% of them were assigned with a different phenotype (normal or DPD deficient) based on the analysis of their two samples. For those having at least one non-compliant sample, this percentage increased up to 33.8%. The moment of blood collection did not affect the DPD phenotyping result. CONCLUSION: Caution should be taken when interpreting U concentrations if the time before centrifugation exceeds 1 h at RT, since it rises significantly afterwards. Not respecting the pre-analytical conditions for DPD phenotyping increases the risk of DPD status misclassification

Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency.

AIMS: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient's uracil (U) plasma concentration is mandatory before fluoropyrimidine (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH2 ) concentrations, as they are essential in reliable DPD-deficiency testing. METHODS: U and UH2 concentrations were collected from 14 hospital laboratories. Stability in whole blood and plasma after centrifugation, the type of anticoagulant and long-term plasma storage were evaluated. The variation induced by time and temperature was calculated and compared to an acceptability range of ±20%. Inter-occasion variability (IOV) of U and UH2 was assessed in 573 patients double sampled for DPD-deficiency testing. RESULTS: Storage of blood samples before centrifugation at room temperature (RT) should not exceed 1 h, whereas cold (+4°C) storage maintains the stability of uracil after 5 hours. For patients correctly double sampled, IOV of U reached 22.4% for U (SD = 17.9%, range = 0-99%). Notably, 17% of them were assigned with a different phenotype (normal or DPD-deficient) based on the analysis of their two samples. For those having at least one non-compliant sample, this percentage increased up to 33.8%. The moment of blood collection did not affect the DPD phenotyping result. CONCLUSION: Caution should be taken when interpreting U concentrations if the time before centrifugation exceeds 1 hour at RT, since it rises significantly afterwards. Not respecting the pre-analytical conditions for DPD phenotyping increases the risk of DPD status misclassification

SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

International audienceHow infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after SARS-CoV-2 Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of the COVID-19 mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reactions, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with a marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies

Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Summary How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies