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Clocchiatti A.,Universita` Degli Studi Of Udine | Clocchiatti A.,Massachusetts General Hospital | Di Giorgio E.,Universita` Degli Studi Of Udine | Viviani G.,Universita` Degli Studi Of Udine | And 5 more authors.
Journal of Cell Science | Year: 2015

The myocyte enhancer factor 2 and histone deacetylase (MEF2- HDAC) axis is a master regulator of different developmental programs and adaptive responses in adults. In this paper, we have investigated the contribution of the axis to the regulation of epithelial morphogenesis, using 3D organotypic cultures of MCF10A cells as a model. We have demonstrated that MEF2 transcriptional activity is upregulated during acini formation, which coincides with exit from the proliferative phase. Upregulation of the transcription of MEF2 proteins is coupled to downregulation of HDAC7, which occurs independently from changes in mRNA levels, and proteasome- or autophagymediated degradation. During acini formation, the MEF2-HDAC axis contributes to the promotion of cell cycle exit, through the engagement of the CDK inhibitor CDKN1A. Only in proliferating cells can HDAC7 bind to the first intron of the CDKN1A gene, a region characterized by epigenetic markers of active promoters and enhancers. In cells transformed by the oncogene HER2 (ERBB2), acini morphogenesis is altered, MEF2 transcription is repressed and HDAC7 is continuously expressed. Importantly, reactivation of MEF2 transcriptional activity in these cells, through the use of a HER2 inhibitor or by enhancing MEF2 function, corrected the proliferative defect and re-established normal acini morphogenesis. © 2015. Source

Pittino F.,Universita` Degli Studi Of Udine | Selmi L.,Universita` Degli Studi Of Udine
Computer Methods in Applied Mechanics and Engineering | Year: 2014

We specialize the Control Volume Finite Element Method (CVFEM) for the solution of the Poisson-Boltzmann and Poisson-Nernst-Planck (also known as Poisson-drift-diffusion) system of equations on unstructured 3D meshes describing nanoelectronic biosensors operated in the DC and AC small signal regimes. We provide the exact analytical expressions for volume and surface integrals derived by means of a linear coordinate transformation and show that they are both accurate and efficient, especially on coarse grids. Being of great importance for the chosen application, the conservation property is investigated and we show that, for the CVFEM to be conservative, the calculations on the boundary have to be performed with special care. CVFEM is carefully compared to the Galerkin Finite Element Method (GFEM) from the point of view of the underlying theory, implementation and solution calculation. The simulation tool is used to evaluate the response of a real nanoelectrode-based biosensor array to the introduction of small nanoparticles. © 2014 Elsevier B.V. Source

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