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Conflicting data are reported on the relationship between hyperglycaemia, diabetesand SIRT6 expression. To elucidate hyperglycaemia-induced molecular mechanisms regulating SIRT6 expression, the effect of hyperglycaemia on DNA methylation and SIRT6 expressionhas been evaluated in human aortic endothelial cells exposed to high glucose. DNA methylation of SIRT6 and any potential clinical implication was also evaluated in type 2 diabeticpatients and compared with healthy controls. Endothelial cells exposed to high glucose showed lower methylation levels in SIRT6 promoter and increased SIRT6 and TET2 expression. The high glucose-induced epigenetic changes persisted after 48 h of glucose normalization. Diabetic patients showed lower levels of SIRT6 DNA methylation compared withnondiabetic patients. SIRT6 DNA methylation levels inversely correlated with plasma glucose. Our results firstly demonstrate the involvement of epigenetic mechanisms in regulating SIRT6 expression. Further experiments are necessary to clarify metabolic memory mechanisms driving to diabetic complications and how SIRT6 is potentially involved.

In this paper, the application of Artificial Neural Networks to perform the thermal calibration of bias for Micro Electro-Mechanical gyros that are installed in Inertial Measurement Units is discussed. In recent years, the interest in using these systems to perform integrated inertial navigation has increased. Several new applications, related to the use of autonomous systems and personal navigation systems in GPS-challenging environments, have been developed. Thermal calibration of bias is a key issue to be assessed to achieve the best performance of a Micro Electro-Mechanical gyro. It can reduce sensor bias to one order of magnitude lower than non-calibrated conditions. Usually, thermal calibration is performed by exploiting polynomial fitting, i.e. finding the least-square polynomial that fits experimental data collected during laboratory tests in a climatic chamber. Polynomials have some drawbacks when they are applied to Micro Electro-Mechanical gyro calibration. They are not adequate to model abrupt change of bias trend in small temperature intervals and sensor hysteresis. For this reason, in the present paper, the use of Back Propagation Artificial Neural Networks is suggested as an improvement of polynomial fitting. Indeed, Neural Networks have intrinsic adaptive configurations and standard training and testing techniques, so that they can be adequately adopted for mapping thermal bias variations. In this paper, the polynomial fitting and Neural Network compensation algorithms are compared on selected testing points where the two techniques have the largest difference. Results highlight that the proposed method has better performance on these points. Therefore, the time in which the flight attitude accuracy meets the requirements imposed by the current regulations is improved by 20%.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers. Importantly, we demonstrate that the treatment of BM-MSCs with a nuclease-resistant RNA aptamer against platelet-derived growth factor receptor ? (PDGFR?) causes the inhibition of receptor-dependent signaling pathways thus drastically hampering BM-MSC recruitment towards TNBC cell lines and BM-MSCs trans-differentiation into carcinoma-associated fibroblast (CAF)-like cells. Moreover, in vivo molecular imaging analysis demonstrated the aptamer ability to prevent BM-MSCs homing to TNBC xenografts. Collectively, our results indicate the anti-PDGFR? aptamer as a novel therapeutic tool to interfere with BM-MSCs attraction to TNBC providing the rationale to further explore the aptamer in more complex pre-clinical settings.