The long noncoding RNA Wisper controls cardiac fibrosis and remodeling

Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we identified Wisper (Wisp2 super-enhancer–associated RNA) as a cardiac fibroblast–enriched lncRNA that regulates cardiac fibrosis after injury. Wisper expression was correlated with cardiac fibrosis both in a murine model of myocardial infarction (MI) and in heart tissue from human patients suffering from aortic stenosis. Loss-of-function approaches in vitro using modified antisense oligonucleotides (ASOs) demonstrated that Wisper is a specific regulator of cardiac fibroblast proliferation, migration, and survival. Accordingly, ASO-mediated silencing of Wisper in vivo attenuated MI-induced fibrosis and cardiac dysfunction. Functionally, Wisper regulates cardiac fibroblast gene expression programs critical for cell identity, extracellular matrix deposition, proliferation, and survival. In addition, its association with TIA1-related protein allows it to control the expression of a profibrotic form of lysyl hydroxylase 2, implicated in collagen cross-linking and stabilization of the matrix. Together, our findings identify Wisper as a cardiac fibroblast–enriched super-enhancer–associated lncRNA that represents an attractive therapeutic target to reduce the pathological development of cardiac fibrosis in response to MI and prevent adverse remodeling in the damaged heart

Experimental and numerical analysis of interply porosities in composites thermoforming

Effective forming of Continuous Fiber Reinforced Thermoplastic Composites requires a detailed understanding and modeling of the forming mechanisms and the development of computational techniques for process simulation. A re-compaction stage is performed at the end of the process in order to avoid interply porosities. The through the thickness behaviour of the composite during forming and consolidation is analysed by a shell finite element with pinching degrees of freedom. This element avoids a locking due to pinching by a modification of the constitutive relation

Analyse expérimentale et simulation numérique de la reconsolidation lors de la mise en forme des CFRTP

International audienceUne expérience de formage montre que de nombreuses porosités sont induites dans un multipli à fibres continues et matrice thermoplastique pendant la mise en forme. Il est essentiel pour la qualité de la pièce finale qu'une phase de reconsolidation efficace termine la fabrication. Dans cette étape, un effort de compression suffisant doit être appliqué de sorte que la contrainte normale transverse dans chaque pli amène la consolidation. Dans l'objectif de prévoir la consolidation par simulation du procédé, un élément fini de coque à contrainte transverse est proposé pour la modélisation de chaque pli. La comparaison d'une simulation de mise en forme dans le cas d'une pièce en Z montre que la contrainte transverse calculée est en bonne corrélation avec la présence ou non de porosités observés expérimentalement

Nitrogen isotopic composition as a gauge of tumor cell anabolism-to-catabolism ratio

Studies have suggested that cancerous tissue has a lower 15N/14N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the 15N/14N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, 15N/14N was negatively correlated with tumor cell density. The magnitude of 15N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations in the anabolism-to-catabolism ratio. However, tumor 15N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support 15N/14N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells