Les États-Unis face à la francophonie : les stratégies américaines en Afrique francophone, 1960-1970

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Silencing mutated β-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating β-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target. Similar to patient tumor specimen the H295 cell line derived from an ACC harbors a natural activating β-catenin mutation. We herein assess the in vitro and in vivo effect of β-catenin inactivation using a doxycyclin (dox) inducible shRNA plasmid in H295R adrenocortical cancer cells line (clone named shβ). Following dox treatment a profound reduction in β-catenin expression was detectable in shβ clones in comparison to control clones (Ctr). Accordingly, we observed a decrease in Wnt/βcatenin-dependent luciferase reporter activity as well as a decreased expression of AXIN2 representing an endogenous β-catenin target gene. Concomitantly, β-catenin silencing resulted in a decreased cell proliferation, cell cycle alterations with cell accumulation in the G1 phase and increased apoptosis in vitro. In vivo, on established tumor xenografts in athymic nude mice, 9 days of β-catenin silencing resulted in a significant reduction of CTNNB1 and AXIN2 expression. Moreover, continous β-catenin silencing, starting 3 days after tumor cell inoculation, was associated with a complete absence of tumor growth in the shβ group while tumors were present in all animals of the control group. In summary, these experiments provide evidences that Wnt/β-catenin pathway inhibition in ACC is a promising therapeutic target

Assessing seasonal and interannual changes in carbonate chemistry across two time-series sites in the North Western Mediterranean Sea

Sustained time-series measurements are crucial to understand changes in oceanic carbonate chemistry. In the North Western Mediterranean Sea, the temporal evolution of the carbonate system is here investigated based on two 10-year time-series (between January 2010 and December 2019) of monthly carbonate parameters measurements at two sampling sites in the Ligurian Sea (ANTARES and DYFAMED). At seasonal timescale, the seawater partial pressure of CO2 (pCO2) within the mixed layer is mostly driven by temperature at both sites, and biological processes as stated by the observed relationships between total inorganic carbon (CT), nitrate and temperature. This study suggests also that mixing and water masses advection could play a role in modulating the CT content. At decadal timescale, significant changes in ocean chemistry are observed with increasing trends in CT (+3.2 ± 0.9 µmol.kg−1.a−1 – ANTARES; +1.6 ± 0.8 µmol.kg−1.a−1 – DYFAMED), associated with increasing pCO2 trends and decreasing trends in pH. The magnitude of the increasing trend in CT at DYFAMED is consistent with the increase in atmospheric pCO2 and the anthropogenic carbon transport of water originating from the Atlantic Ocean, while the higher trends observed at the ANTARES site could be related to the hydrological variability induced by the variability of the Northern Current

The Impact of a Pandemic Event on Mortality Risk for Protection Insurance

International audienceRecent events such as influenza A (H1N1), dengue or cholera viruses, have reminded insurers that they could suffer the occurrence of a pandemic risk. A severe pandemic event could cause a significant increase in mortality, and consequently might cause the bankruptcy of insurance companies. This article focuses on death guarantee for Protection business, and its aim is to determine how to model the impact of a pandemic event on mortality risk, by taking into account the type of available data. To do so, mortality risk is split into a trend and a pandemic shock event. It is possible to calibrate this shock for particular viruses, for example influenza virus. The last section briefly presents some possible extensions in the framework of stochastic modelling in connection with AIDS dynamic evolution

Evolution of a novel left-right asymmetry involving tissue remodelling and MyoID

Left-right asymmetries recurrently evolve in animals but the underlying developmental mechanisms are unknown. In most Drosophila species, the male genitalia is symmetric and undergoes a clockwise 360° rotation during development. In D. melanogaster, this tissue remodeling process is directed by class I myosins: in MyoID mutants the rotation is reversed and the genitalia remains symmetric. Males of Drosophila pachea have evolved unique left-right asymmetric genital organs and a characteristic right-sided copulation posture in the past 3-6 million years. To test if these asymmetries in morphology and behavior evolved via the recruitment of pre-existing directional cues controlled by MyoID, we used CRISPR to knockout MyoID in D. pachea. Strikingly, mutant males undergo a reverse genitalia rotation and develop mirror-image asymmetric genitalia, indicating that MyoID controls both the direction of genitalia rotation direction and morphological asymmetry. Although genital asymmetry is reversed, MyoID mutants still adopt a wild-type right-sided copulation posture. Our results show that MyoID and its asymmetry guidance role were recruited for the evolution of a novel left-right asymmetry in D. pachea and that lateralized copulation behavior is determined by other mechanisms. The evolution of a new left-right organ size asymmetry in D. pachea involved recruitment of existing directional cues

A novel mechanism for left-right asymmetry establishment involving tissue remodeling and MyoID

How novel left-right asymmetries evolve in animals is unknown. Drosophila pachea males display a unique left-right asymmetry in the genital organs and mate in a right-sided position onto the female. In flies, male genitalia undergo a clockwise 360° rotation during development. To test if this tissue remodeling process is linked to asymmetry development in the male genitalia of Drosophila pachea, w e developed CRIPSR and transgenesis in this singular species. As in D. melanogaster , mutants of the MyoID gene homolog undergo reverse rotation of the developing genitalia. In addition, they have mirror-image asymmetric genitalia. Although their genital asymmetry is reversed mutants still adopt a right-sided copulation posture. Our results reveal a novel mechanism for establishing left-right asymmetry in animals, involving complex tissue remodeling and MyoID. One Sentence Summary D. pachea genital left-right size asymmetry is established through MyoID-mediated tissue remodelling and does not determine the direction of mating posture

Oxygen budget for the north-western Mediterranean deep-convection region

The north-western Mediterranean deep convection plays a crucial role in the general circulation and biogeochemical cycles of the Mediterranean Sea. The DEWEX (DEnse Water EXperiment) project aimed to better understand this role through an intensive observation platform combined with a modelling framework. We developed a 3 dimensional coupled physical and biogeochemical model to estimate the cycling and budget of dissolved oxygen in the entire north-western Mediterranean deep convection area over the period September 2012 to September 2013. After showing that the simulated dissolved oxygen concentrations are in a good agreement with the in situ data collected from research cruises and Argo floats, we analyze the seasonal cycle of the air-sea oxygen exchanges, as well as physical and biological oxygen fluxes, and we estimate an annual oxygen budget. Our study indicates that the annual air-to-sea fluxes in the deep convection area amounted to 20 mol m−2 yr−1. 88 % of the annual uptake of atmospheric oxygen, i.e. 18 mol m−2, occurred during the intense vertical mixing period. The model shows that an amount of 27 mol m−2 of oxygen, injected at the sea surface and produced through photosynthesis, was transferred under the euphotic layer, mainly during deep convection. An amount of 20 mol m−2 of oxygen was then gradually exported in the aphotic layers to the south and west of the western basin, notably, through the spreading of dense waters recently formed. The decline in the deep convection intensity in this region predicted by the end of the century in recent projections, may have important consequences on the overall uptake of atmospheric oxygen in the Mediterranean Sea and on the oxygen exchanges with the Atlantic Ocean, that appear necessary to better quantify in the context of the expansion of low-oxygen zones

Impact of mismatch repair deficiency on tumour regression grade after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma

International audienceBackground: The use of neoadjuvant chemotherapy (NAC) in patients with mismatch repair (MMR) deficient (dMMR) localized gastric and oeso-gastric junction (OGJ) adenocarcinoma is subject of debate. Histological response assessment might help to better evaluate the impact of dMMR on response to NAC.Methods: Patients with localized gastric/OGJ adenocarcinoma resected after NAC were retrospectively identified. MMR protein expression status was assessed by immunohistochemistry. The primary objective was the frequency of histological responders to NAC defined by tumour regression grade (TRG) using Mandard's (TRG1-2) and Becker's (TRG1) classifications, according to the MMR status.Results: In total, 247 patients with 43 dMMR and 204 pMMR gastric/OGJ adenocarcinoma were identified. Among dMMR tumours, 18 (42%) arose from the OGJ. Histological response (Becker TRG1-2) was observed for 28% and 35% of dMMR and pMMR tumours, respectively (p = 0.35). Similar results were observed with Mandard classification. With a median follow-up of 37.5 months, median disease-free and overall survival were not reached for the dMMR group.Conclusion: Histological response after NAC in patients with localized dMMR gastric/OGJ adenocarcinoma is not statistically different to those with pMMR tumours. This study provides additional data for the discussion about avoiding NAC in patients with dMMR gastric/OGJ adenocarcinomas

CD34 and FSHR Expression to Differentiate Multiple Subtypes of Benign and Malignant Renal Neoplasms

BackgroundCurrently, no markers accurately differentiate benign from malignant renal masses. CD34 and FSHR are transmembrane proteins involved in neo-angiogenetic pathways and are differently expressed in several normal and cancerous tissues. However, little evidence exists on their distribution in different renal tumors. We aimed to evaluate their expressions in various renal tumors and adjacent normal tissue.MethodsWe retrieved 810 histological samples from 26 patients who underwent surgery for suspected RCa. In each case a core of 10 × 1 mm was selected perpendicular to the tumor capsule between normal kidney and tumor. Within this core 30 regions of interest (ROI), each measuring 669 μm × 500 μm, were acquired at 20× magnification (n = 2 adjacent normal tissue; n = 2 tumor capsule; n = 26 tumor). The surface area of FSHR and CD34 immunostaining was quantified in each ROI using number of stained pixels. The results were compared between RCa and normal kidney.ResultsImmunostaining was significantly different in normal, tumor capsular, and tumor tissues (both CD34 and FSHR P 0.9). The correlation amongst levels of staining in tumor tissues and distance from the capsule were overall weak (Spearman coefficient CD34 to 0.0644; FSHR-0.16322).ConclusionCD34 and FSHR are differentially expressed across renal tumor subtypes and between tumor and surrounding tissues. FSHR expression alone may be a useful tool to differentiate benign from malignant tumors and chromophobe carcinoma from oncocytoma