STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect

A partition method for the solution of coupled liquid-structure interaction problem

A numerical code is presented to study the motion of an incompressible inviscid flow in a deformable tank. It is based on a method belonging to the partition treatment class, as the fluid and structural fields are solved by coupling two distinct models. The fluid field is modeled by the Laplace equation and numerically solved by a Finite Volume technique. The computational grid is updated at each time step to take into account the movements of the free surface and the deformations of the vertical walls. An unsteady finite element formulation is used for modeling the tank on a grid discretized by triangular elements and linear shape functions. Results are presented for two different cases: a flow induced by a perturbation on the free surface in a tank motionless; a flow in a tank forced to oscillate periodically in the horizontal direction

Use of Robotics kits for the enhancement of metacognitive skills of mathematics: a possible approach

The present study is aimed at analyzing the process of building and programming robots as a metacognitive tool of mathematics. Quantitative data from a study performed on a sample of students attending an Italian secondary school are described. Results showed that robotics activities may be used as a new metacognitive environment allowing students to improve their attitude towards mathematics, and to increase their attitude to reflect on themselves and on their own learning, and their higher-level control components, such as forecasting, planning, monitoring and evaluation exercises and problems related to implementation

QCALT: a tile calorimeter for KLOE-2 upgrade

The upgrade of the DA$\Phi$NE machine layout requires a modification of the size and position of the inner focusing quadrupoles of KLOE-2 thus asking for the realization of two new calorimeters covering the quadrupoles area. To improve the reconstruction of $K_L\to 2\pi^0$ events with photons hitting the quadrupoles a calorimeter with high efficiency to low energy photons (20-300 MeV), time resolution of less than 1 ns and space resolution of few cm, is needed. To match these requirements, we are designing a tile calorimeter, QCALT, where each single tile is readout by mean of SiPM for a total granularity of 2400 channels. We show first tests of the different calorimeter components

Modelling and experimental characterization of secondary suspension elements for rail vehicle ride comfort simulation

Secondary suspensions play an essential role in the dynamic behaviour of rail vehicles. In particular, they are adopted to reduce the vibrations transmitted to the carbody, thus improving ride comfort. In this paper, an experimental characterization of the viscous damper and coil spring elements composing a vertical secondary suspension is presented. The elements are separately tested with the aim of analysing their dynamic behaviour. Then, modified prototypes are manufactured to reduce the transmitted force. The results of the experimental campaign are later adopted to tune the parameters of the mathematical model of the whole secondary suspension, including the dynamics of both the coil spring and the damper elements. This model allows discussing the effectiveness of the proposed modifications, proving the design of both the components to be fundamental for the improvement of ride comfort

The rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i

Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB

Enhanced high-temperature mechanical behavior of an in situ TiAl matrix composite reinforced with alumina

A Ti-45Al-3Cr-2.5Nb alloy reinforced with in situ formed alumina has been produced by means of centrifugal casting by adding zirconium oxide in the crucible. The dispersion-strengthened alloy has been characterized to verify its microstructure and particle distribution. Mechanical tests carried out over the temperature range 850-950 degrees C highlighted that in situ formed alumina allows to increase the alloy yield stress by 21% at 850 degrees C and by 35% at 900 degrees C. Moreover, the in situ formed oxide particles produced an increase of the Young's modulus of about 10% at 850 degrees C and of about 8% at 900 degrees C. Considering that the tested alloy has a density that is about a half of nickel superalloys, obtaining high specific mechanical properties over the temperature range 850-950 degrees C can boost its application in the production of turbine blades