On inverse analysis and robustness evaluation for biological structure behaviour in FE simulation. Application to the liver

To prevent abdominal organs traumas, the definition of efficient safety devices should be based on a detailed knowledge of injury mechanisms and related injury criteria. In this sense, FE simulation coupled to experiment could be a valuable tool to provide a better understanding of internal organs behaviour under crash conditions. This work proposes a methodology based on inverse analysis which combines exploration process optimisation and robustness study to obtain mechanical behaviour of the complex structure of the liver through FE simulation. The liver characterisation was build on Mooney Rivlin hyperelastic behaviour law considering whole liver structure under uniform quasi-static compression. With the global method used, the model fits experimental data. The variability induced by modelling parameters is quantified within a reasonable time. Liver compression, FE simulation, inverse analysis, robustness analysis

Seismic and aseismic deformation along the East African Rift System from a reanalysis of the GPS velocity field of Africa

International audienceThe improvement of the geodetic coverage within the African Plate over the last decade together with an extended GPS position time-series allows improved accuracy in determining the velocity field than prior geodetic studies. Using this new velocity field of the whole African continent, the best model proposed here remains consistent with previous studies including the existence of two small plates along the East African Rift System (EARS, Victoria and Rovuma).We focus specifically on the velocities along this plate boundary by estimating both the geodetic and the seismic moment rate.Whereas we use a scalar form of the Kostrov relation to calculate the geodetic moment rate, the seismic moment rate is obtained by integrating the cumulative truncated Gutenberg-Richter earthquake distribution of local events in the 39-yr-long worldwide catalogue, using a maximum likelihood method. This statistical method allows us to take into account the probable incompleteness of the existing catalogue and to assume the seismic moment rate calculated from this short catalogue to be representative of the long-term seismic deformation. The comparison of geodetic and seismic energy release sheds light on the variations of mechanical behaviour related to intracontinental extension along the EARS. The southward increase, observed along the rift, of the proportion of geodetic moment seismically accommodated suggests a significant control of the thermal structure associated with different states of rifting evolution

Ebp1 expression in benign and malignant prostate

<p>Abstract</p> <p>Background</p> <p>ErbB3-binding protein 1 (Ebp1) is a member of the <it>PA2G4 </it>family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression <it>in vivo</it>. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.</p> <p>Methods</p> <p>The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.</p> <p>Results</p> <p>The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.</p> <p>Conclusion</p> <p>Although not related to disease recurrence, this is the first <it>in vivo </it>study to report that Ebp1 expression correlates with PCa progression.</p

O-GlcNAcylation-Inducing Treatments Inhibit Estrogen Receptor α Expression and Confer Resistance to 4-OH-Tamoxifen in Human Breast Cancer-Derived MCF-7 Cells.

PLoS OneInternational audienceO-GlcNAcylation (addition of N-acetyl-glucosamine on serine or threonine residues) is a post-translational modification that regulates stability, activity or localization of cytosolic and nuclear proteins. O-linked N-acetylgluocosmaine transferase (OGT) uses UDP-GlcNAc, produced in the hexosamine biosynthetic pathway to O-GlcNacylate proteins. Removal of O-GlcNAc from proteins is catalyzed by the β-N-Acetylglucosaminidase (OGA). Recent evidences suggest that O-GlcNAcylation may affect the growth of cancer cells. However, the consequences of O-GlcNAcylation on anti-cancer therapy have not been evaluated. In this work, we studied the effects of O-GlcNAcylation on tamoxifen-induced cell death in the breast cancer-derived MCF-7 cells. Treatments that increase O-GlcNAcylation (PUGNAc and/or glucosoamine) protected MCF-7 cells from death induced by tamoxifen. In contrast, inhibition of OGT expression by siRNA potentiated the effect of tamoxifen on cell death. Since the PI-3 kinase/Akt pathway is a major regulator of cell survival, we used BRET to evaluate the effect of PUGNAc+glucosamine on PIP3 production. We observed that these treatments stimulated PIP3 production in MCF-7 cells. This effect was associated with an increase in Akt phosphorylation. However, the PI-3 kinase inhibitor LY294002, which abolished the effect of PUGNAc+glucosamine on Akt phosphorylation, did not impair the protective effects of PUGNAc+glucosamine against tamoxifen-induced cell death. These results suggest that the protective effects of O-GlcNAcylation are independent of the PI-3 kinase/Akt pathway. As tamoxifen sensitivity depends on the estrogen receptor (ERα) expression level, we evaluated the effect of PUGNAc+glucosamine on the expression of this receptor. We observed that O-GlcNAcylation-inducing treatment significantly reduced the expression of ERα mRNA and protein, suggesting a potential mechanism for the decreased tamoxifen sensitivity induced by these treatments. Therefore, our results suggest that inhibition of O-GlcNAcylation may constitute an interesting approach to improve the sensitivity of breast cancer to anti-estrogen therapy

Prevention of infertility : recognizing and targeting numerous risk factors.

editorial reviewedFollow-up consultations in gynaecology and general practice offer valuable opportunities to discuss fertility and the importance of a pre-conceptional assessment before attempting pregnancy. During these consultations, it is vital for healthcare professionals to provide patients with essential information about considerations before conceiving a child. Additionally, it is important to educate patients about basic hygiene practices that can impact both male and female fertility. The prevention of fertility disorders requires a holistic approach identifying and targeting numerous risk factors.Les consultations de suivi en gynécologie et en médecine générale offrent des opportunités précieuses pour discuter de la fertilité et de l’importance d’une évaluation préconceptionnelle avant toute tentative de grossesse. Au cours de ces consultations, il est primordial pour les professionnels de santé de fournir aux patients des informations essentielles concernant les aspects à considérer avant de concevoir un enfant. De plus, il convient de sensibiliser les patients aux pratiques d’hygiène de base qui peuvent avoir un impact sur la fertilité masculine et féminine. La prévention des troubles de la fertilité nécessite une approche holistique identifiant et ciblant de nombreux facteurs de risque

Is the typicality of “Provence Rosé wines” only a matter of color?

Aims: Given the diversity of French dry Rosé wines, Provence Rosé producers (France) wish to evaluate the typicality of their wines in order to better identify their typical characteristics. A clear pink color is one of them but they would also like to identify some specific odors and aromas. Here, we address these issues by: (i) assessing whether the identity of Provence Rosé wines is perceptible by tasting and shared by professionals based on specific odors and aromas (disregarding color as indicator using black glasses), and (ii) evaluating the impact of color on Provence Rosé wine typicality. Methods and results: Complementary methods were used: exemplarity measurements by a panel of wine professionals, sensory evaluation by a trained expert panel, and color assessment. It was confirmed that Provence Rosé wine typicality is based on color because the clearest wines were found to be more typical. However, typicality in odors and aromas was also demonstrated. Using black glasses, wine professionals from Provence agreed on ‘citrus fruit’, ‘exotic fruit’ and ‘fresh floral’ odors and aromas being typical attributes of Provence Rosé wines. Next, when using transparent glasses, the color of the wines clearly modified the perception of exemplarity. Conclusion: There is no single sensory profile of typical Provence Rosé wines. Variability within the sensory profiles of this specific Rosé wine area was observed, but some common aromatic and visual characteristics were identified. Significance and impact of the study: These results could be used as a marketing tool to better highlight the specific intrinsic characteristics of Provence Rosé wines. It will now be interesting to investigate the Provence area further in order to evaluate potential sub-area specificities linked to “terroir” factors

Integrin Alpha 8 Recessive Mutations Are Responsible for Bilateral Renal Agenesis in Humans

Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease