Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.     

Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia

Lesions issued from the ischemia/reperfusion (I/R) stress are a major challenge in human pathophysiology. Of human organs, the kidney is highly sensitive to I/R because of its high oxygen demand and poor regenerative capacity. Previous studies have shown that targeting the hypusination pathway of eIF5A through GC7 greatly improves ischemic tolerance and can be applied successfully to kidney transplants. The protection process correlates with a metabolic shift from oxidative phosphorylation to glycolysis. Because the protein kinase B Akt is involved in ischemic protective mechanisms and glucose metabolism, we looked for a link between the effects of GC7 and Akt in proximal kidney cells exposed to anoxia or the mitotoxic myxothiazol. We found that GC7 treatment resulted in impaired Akt phosphorylation at the Ser473 and Thr308 sites, so the effects of direct Akt inhibition as a preconditioning protocol on ischemic tolerance were investigated. We evidenced that Akt inhibitors provide huge protection for kidney cells against ischemia and myxothiazol. The pro-survival effect of Akt inhibitors, which is reversible, implied a decrease in mitochondrial ROS production but was not related to metabolic changes or an antioxidant defense increase. Therefore, the inhibition of Akt can be considered as a preconditioning treatment against ischemia.     

Theoretical and Kinetic Analysis of the Esterification of Undecylenic Acid with Glycerol

The synthesis of undecylenic acid partial esters can be performed at mild temperature with a classical esterification reaction catalyzed by dodecylbenzene sulfonic acid (DBSA). A semi-empirical molecular modeling on the different reaction intermediates indicates that DBSA can strongly decrease their heats of formation through hydrogen bonding. Diester formation seems to be thermodynamically favored with a selectivity for alpha, alpha, or alpha, beta forms that depend on the geometry of the catalyst-intermediate configuration. Triesters are not favored but a high selectivity for monoesters requires a kinetic control. Experimental approach, considering different DBSA concentrations and temperature partially confirms the theoretical predictions but surfactant properties of DBSA and monoesters may induce nonpredicted geometries. Global apparent activation energies are calculated, corresponding to the formation and hydrolysis of mono and diesters. If water trapping allows the decrease of hydrolysis reaction constants, the presence of water and subsequent phase separation may explain differences between theoretical and experimental results and could help increasing monoester selectivity.     

Perfluorinated coatings and terracotta: An impregnation study

The mechanisms of penetration onto terracotta of two commercially available perfluorinated acrylates were studied: Zonyl®225, a solvent‐based perfluorinated polyacrylate containing two unfluorinated acrylic or vinylic monomers; and Zonyl®329, an aqueous dispersion synthesized from comparable monomers plus a vinylic silane. Two application methods were used: by immersion of the substrate for 15 h and by multiple brush strokes, with pauses between strokes. Application effectiveness was assessed by measuring the depth of penetration into terracotta. The results of coating were examined by optical and electron microscopy, including elemental analysis. When the impregnating agent was applied by extended immersion, both solvent‐based and aqueous dispersion exhibited higher penetration depths with increasing concentrations. When applied using multiple brush strokes, the solvent‐based solution exhibited the same trend as that in immersion; however, the aqueous dispersion showed no penetration beyond ～ 0.12 mm. This limited depth of penetration is shown to be a result of partial drying between brush strokes, but also as a result of porosity restrictions and electrostatic interactions between the positively charged polymer colloids in the dispersion and the negatively charged terracotta surface. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Dynamic Delaunay tetrahedralisation of a deforming surface

Reconstruction algorithms make it possible to retrieve a surface from the Delaunay tetrahedralisation (DT) of a point sampling, whose density reflects the surface local geometry and thickness. Most of these algorithms are static and some work remains to be done to handle deforming surfaces. In such case, we defend the idea that each point of the sampling should move with the surface using the information given by the motion to allow fast reconstruction. In this article, we tackle the problem of producing a good evolving sampling of a deforming surface S, and maintaining its DT along the motion. The surface is known only through a projection operator (O ₁):ℝ³→S, and a normal operator (O ₂) that returns the oriented normal at a point on the surface. On that basis, we offer some perspectives on how reconstruction algorithms can be extended to the tracking of deforming surfaces.     

Continuous–discrete adaptive observers for state affine systems

The observation of a class of multi-input multi-output (MIMO) state affine systems with constant unknown parameters and discrete time output measurements is addressed. Assuming some persistent excitation conditions to hold and the sampling steps to satisfy some boundedness hypotheses, system observability is ensured and a class of global exponential observers is synthesized.     

Influence of pregnancy on the outcome of breast cancer: a case-control study. Societe Francaise de Senologie et de Pathologie Mammaire Study Group

The relationship between pregnancy and the outcome of breast cancer remains controversial. The purpose of this study was to determine the prognostic value of pregnancy at the time of diagnosis of primary infiltrating breast cancer. In a retrospective multi-center study we compared a group of 154 patients presenting pregnancy-associated (PA) breast cancer with a control group of 308 patients presenting non-pregnancy-associated (non-PA) breast cancer. Classic prognostic factors, treatment modalities, disease-free survival and overall survival were compared in the 2 groups. The relative importance of pregnancy was assessed by Cox multivariate analysis. There was a significantly higher proportion of inflammatory breast cancer, large tumors and negative receptor status in the PA group. Five-year recurrence-free survival, metastasis-free survival and overall survival were lower both in the whole PA group and in the PA sub-group excluding patients with inflammatory breast cancer than in the corresponding non-PA groups. According to clinical stage, histoprognostic grade and microscopic lymph-node involvement, probability of 5-year metastasis-free survival and overall survival was lower in the PA group. Outcome was significantly poorer after chemotherapy for patients in the PA sub-group than in the non-PA sub-group. Multivariate analysis demonstrated that pregnancy was an independent and significant prognostic factor. Pregnancy has an adverse effect on the outcome of breast cancer. Concurrent or recent pregnancy should be taken into account in the development of new systemic therapies. Our findings have important implications for further research into the basic mechanisms of cancer.     

Modeling and Rendering of Heterogeneous Granular Materials: Granite Application

Light‐matter interactions is one of the most important factors of realistic rendering. While a lot of work has already been performed in the light transport and simulation area, we believe that “virtual materials” have not yet been studied enough to achieve a high degree of realism. Some good models exist in order to take into account homogeneous materials. However, there are only a few studies of heterogeneous granular materials. In this paper, we propose a method based on mimicking natural phenomena to take into account these materials. Our study focuses on granite, which can be considered as a heterogeneous agglomerate of individually homogeneous grains. First we present a nucleation/growth process inspired technique giving a full 3D model of granite. Then, we use a rendering process taking into account each material component and subsurface scattering in a simple way.     

Closure Properties of Real Number Classes under CBV Functions

CBV functions are computable real functions of bounded variation. In this paper we investigate the basic properties of CBV functions. We are especially interested in the question of whether a real number class is closed under CBV functions. The real number classes considered here include the classes of computable (EC), semi-computable (SC), weakly computable (WC), divergence bounded computable (DBC) and recursively approximable (RA) real numbers. We show that the classes EC, RA and DBC are closed under CBV functions but SC and WC are not. Furthermore, WC$ is not even closed under computable monotone functions and, finally, the image sets of $\wc$ under computable monotone functions and CBV functions are different.