DNA Damage Stress Control Is a Truncated Large T Antigen and Euchromatic Histone Lysine Methyltransferase 2–Dependent Central Feature of Merkel Cell Carcinoma

International audienceMerkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. Merkel cell polyomavirus causes 80% of MCCs, encoding the viral oncogenes small T and truncated large T (tLT) antigens. These proteins impair the RB1-dependent G1/S checkpoint blockade and subvert the host cell epigenome to promote cancer. Whole-proteome analysis and proximal interactomics identified a tLT-dependent deregulation of DNA damage response (DDR). Our investigation revealed, to our knowledge, a previously unreported interaction between tLT and the histone methyltransferase EHMT2. T antigen knockdown reduced DDR protein levels and increased the levels of the DNA damage marker γH2Ax. EHMT2 normally promotes H3K9 methylation and DDR signaling. Given that inhibition of EHMT2 did not significantly change the MCC cell proteome, tLT-EHMT2 interaction could affect the DDR. With tLT, we report that EHMT2 gained DNA damage repair proximal interactors. EHMT2 inhibition rescued proliferation in MCC cells depleted for their T antigens, suggesting impaired DDR and/or lack of checkpoint efficiency. Combined tLT and EHMT2 inhibition led to altered DDR, evidenced by multiple signaling alterations. In this study, we show that tLT hijacks multiple components of the DNA damage machinery to enhance tolerance to DNA damage in MCC cells, which could explain the genetic stability of these cancers

Elevational range shifts among Bombina toad populations in the Alps in response to future climate change

International audienceThe ability of species to cope with climate change depends on both intrinsic and extrinsic factors, for instance dispersal ability and landscape composition. Nevertheless, populations can also differ in their ability to track the shift of suitable areas due to traits developed in response to local environmental pressures. In the south-west part of the distribution area of the yellow-bellied toad (Bombina variegata), two divergent ecotypes, named fast and slow, can be identified along a gradient of anthropization. We investigate the ability of these ecotypes to track the altitudinal shift of suitable habitat in the French Alps at the horizon 2100. First, we modelled future climatic suitability in the Alps according to climatic scenarios, and then we used a process-based model simRShift, to simulate the demographic and colonisation processes in the future accounting for the traits of each ecotype. The fast ecotype may not persist and colonise as many habitats compared to the slow ecotype (e.g. 872.3km2 and 4200.2 km2 under the optimistic scenario in 2100 for the GFDL-ESM4 GCM respectively for fast and slow). We explain these results by the shorter lifespan of the fast ecotype that makes it more vulnerable to stochasticity

The anisotropy of 2D or 3D Gaussian random fields through their Lipschitz-Killing curvature densities

International audienceWe are interested here in modeling and estimating the anisotropy of 2D and 3D Gaussian random fields through the geometry of their excursion sets. In order to do this, we use Lipschitz-Killing curvatures of the level sets as functions of the levels and see them as generalized processes for which we are able to obtain a joint functional Central Limit Theorem. For 2D and 3D stationary Gaussian fields we provide explicit formulas for the Lipschitz-Killing curvature densities from which we can deduce geometrical equivalent of second spectral moments and anisotropy ratios that allow the estimation of the anisotropy of the underlying Gaussian field

Improving the thermoelectric performance of scandium nitride thin films by implanting helium ions

International audienceIon implantation is a widely used technique to introduce defects in low-dimensional materials and tune their properties. Here, we investigate the thermoelectric properties of scandium nitride thin films implanted with helium ions, revealing a positive impact of defect engineering on thermoelectric performance. Transport properties modeling and electron microscopy provide insights on the defect distribution in the films. The electrical resistivity and Seebeck coefficient increase significantly in absolute values after implantation and partially recover upon annealing as some of the implantation-induced defects heal. The thermal conductivity decreases by 46 % post- implantation due to the formation of extended defects and nanocavities. Consequently, the thermoelectric figure of merit zT doubles for the sample annealed at 673 K. These findings highlight the potential of controlled ion implantation to enhance thermoelectric properties in thin films, paving the way for further optimization through defect engineering

Elevage de poulets biologiques: Contraintes et leviers de développement

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Les fruits du gattilier permettent-ils de diminuer les comportements sexuels et agressifs des porcs mâles non castrés ?

International audienceCould chasteberry fruits reduce mounting and aggressive behaviors of uncastrated male pigs?Mounting and aggressive behaviors of uncastrated male pigs may lead to injuries and affect their welfare. Chasteberry (Vitex agnus castus), a shrub from Mediterranean areas, could lower the libido of males. In a previous study, we showed that uncastrated boars fed with 10g per day of chasteberry fruits powder during fattening had lower mounting behaviors and testosterone concentrations than control. However, this result was not repeated. Our aim was to evaluate if increasing doses of chasteberry fruits powder during pig fattening could reduce sexual and aggressive behaviors. A group of 28 boars were fed with 10g per animal and per day of chasteberry fruits powder from 112 days of age (60kg on average) to 135 days of age, 15g until 155 days of age and 20g until slaughtering (120kg on average). The control group of 27 boars did not receive chasteberry. Blood and saliva samples were collected at 170 days of age for testosterone and cortisol concentrations analysis. The average feed intake and daily weight gain were not different between groups. The number of aggressive behaviors was significantly lower in the group fed with chasteberry than in the control group. The number of mounting behaviors and the plasma and saliva cortisol concentrations were not different between groups. Contrary to our previous results, plasma and saliva testosterone concentrations were higher in the chasteberry compared to the control group, probably due to differences in the composition of chasteberry batches. In conclusion, feeding uncastrated male pigs with chasteberry fruits powder significantly reduced aggressive behaviors with no effect on feed intake, daily weight gain and plasma and saliva cortisol levels.Suite à l’interdiction de la castration à vif des porcelets, certains éleveurs élèvent des porcs mâles non castrés, qui expriment des comportements sexuels de chevauchement entrainant des blessures et des comportements agressifs altérant leur bien-être. Le gattilier (Vitex agnus-castus) est une plante utilisée par les moines au Moyen-âge pour son effet anaphrodisiaque. Nous avons précédemment montré que la distribution d’une dose fixe de poudre de fruits de gattilier (10g par animal et par jour) à des porcs mâles non castrés pendant l’engraissement diminuait les comportements de chevauchement, mais ce résultat n’a pas pu être répété (Vanbauce et al., JRP 2023). L’objectif de cette expérimentation était de vérifier si la distribution d’une dose croissante de gattilier au cours de l’engraissement permettait de diminuer significativement les comportements de chevauchement et d’agressivité. Pour cela, un lot de 28 porcs a reçu une dose quotidienne croissante de poudre de fruits de gattilier : 10g par porc et par jour de 112 jours d’âge (60kg en moyenne) à 135 jours d’âge, 15g jusqu’à 155 jours d’âge et 20g jusqu’à l’abattage (120kg en moyenne). Un lot témoin de 27 porcs ne recevait pas de gattilier. Nous avons suivi la consommation moyenne, le poids vif et le nombre de chevauchements et d’agressions avec 15 minutes d’observation matin et soir un jour par semaine. Des prélèvements de sang et de salive ont été réalisés à 150 jours d’âge pour mesurer les taux de testostérone et cortisol. Le nombre de bagarres était significativement plus faible dans le lot consommant le gattilier que dans le lot témoin (p<0,05), le nombre de chevauchements n’était pas significativement différent. L’analyse des concentrations de testostérone et de cortisol est en cours

Avances recientes en la formación y calidad de la cáscara de los huevos

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Neural correlates of communication modes in medical students using fMRI

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Les outils de patrimonialisation des biens culturels - Focus sur la marque et le droit sur l'image des domaines nationaux

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Evaluation of serum mid-infrared spectroscopy as new prognostic marker for first-line bevacizumab-based chemotherapy in metastatic colorectal cancer

International audienceBackground and aims: Bevacizumab-based chemotherapy is a recommended first-line treatment for metastatic colorectal cancer (mCRC). Robust biomarkers with clinical practice applicability have not been identified for patients with this treatment. We aimed to evaluate the prognostic yield of serum midinfrared spectroscopy (MIRS) on patients receiving first-line bevacizumab-based chemotherapy for mCRC. Methods: We conducted an ancillary analysis from a multicentre prospective study (NCT00489697). All baseline serums were screened by attenuated total reflection method. Principal component analysis and unsupervised k-mean partitioning methods were performed blinded to all patients' data. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: From the 108 included patients, MIRS discriminated two prognostic groups. First group patients had significantly lower body mass index ( p = 0.026) and albumin levels ( p &lt; 0.001), and higher levels of angiogenic markers, lactate dehydrogenase and carcinoembryonic antigen ( p &lt; 0.001). In univariate analysis, their OS and PFS were shorter with respective medians: 17.6 vs 27.9 months ( p = 0.02) and 8.7 vs 11.3 months ( p = 0.03). In multivariate analysis, PFS was significantly shorter (HR = 1.74, p = 0.025) with a similar trend for OS (HR = 1.69, p = 0.061). Conclusion: By metabolomic fingerprinting, MIRS proves to be a promising prognostic tool for patients receiving first-line bevacizumab-based chemotherapy for mCRC.</div