Evidenze molecolari del ruolo antiproliferativo e pro-apoptotico della clusterina in cellule epiteliali prostatiche umane

The Clusterin (CLU) gene produces different forms of protein products which vary in their biological properties and distribution within the cell. Both the extra- and intracellular CLU forms regulate cell proliferation and apoptosis. Dis-regulation of CLU expression occurs in many cancer types, including prostate cancer. The role that CLU plays in tumorigenesis is still unclear. We found that CLU over-expression inhibited cell proliferation and induced apoptosis in prostate cancer cells. Here we show that depletion of CLU affects the growth of PC-3 prostate cancer cells. Following siRNA, all protein products quickly disappeared, inducing cell cycle progression and higher expression of specific proliferation markers (i.e. H3 mRNA, PCNA and cyclins A, B1 and D) as detected by RT-qPCR and Western blot. Quite surprisingly, we also found that the turnover of CLU protein is very rapid and tightly regulated by ubiquitin–proteasome mediated degradation. Inhibition of protein synthesis by cycloheximide showed that CLU half-life is less than 2 hours. All CLU protein products were found poly-ubiquitinated by co-immuniprecipitation. Proteasome inhibition by MG132 caused stabilization and accumulation of all CLU protein products, strongly inducing the nuclear form of CLU (nCLU) and committing cells to caspase-dependent death. In conclusion, proteasome inhibition may induce prostate cancer cell death through accumulation of nCLU, a potential tumour suppressor factor.

Seismic sequences analysis for estimation of earthquake source parameters: corner frequency, stress drop, and seismic moment observations

The present study has been carried out with the following objectives: i) To investigate the attributes of source parameters of local and regional earthquakes; ii) To estimate, as accurately as possible, M0, fc, Δσ and their standard errors to infer their relationship with source size; iii) To quantify high-frequency earthquake ground motion and to study the source scaling. This work is based on observational data of micro, small and moderate -earthquakes for three selected seismic sequences, namely Parkfield (CA, USA), Maule (Chile) and Ferrara (Italy). For the Parkfield seismic sequence (CA), a data set of 757 (42 clusters) repeating micro-earthquakes (0 ≤ MW ≤ 2), collected using borehole High Resolution Seismic Network (HRSN), have been analyzed and interpreted. We used the coda methodology to compute spectral ratios to obtain accurate values of fc , Δσ, and M0 for three target clusters (San Francisco, Los Angeles, and Hawaii) of our data. We also performed a general regression on peak ground velocities to obtain reliable seismic spectra of all earthquakes. For the Maule seismic sequence, a data set of 172 aftershocks of the 2010 MW 8.8 earthquake (3.7 ≤ MW ≤ 6.2), recorded by more than 100 temporary broadband stations, have been analyzed and interpreted to quantify high-frequency earthquake ground motion in this subduction zone. We completely calibrated the excitation and attenuation of the ground motion in Central Chile. For the Ferrara sequence, we calculated moment tensor solutions for 20 events from MW 5.63 (the largest main event occurred on May 20 2012), down to MW 3.2 by a 1-D velocity model for the crust beneath the Pianura Padana, using all the geophysical and geological information available for the area. The PADANIA model allowed a numerical study on the characteristics of the ground motion in the thick sediments of the flood plain.

Experiments on Pro-Sociality and Environmental Issues

The thesis comprises three essays that use experimental methods, one about other-regarding motivations in economic behavior and the others on pro-social behavior in two environmental economics problems. The first chapter studies how the expectations of the others and the concern to maintain a balance between effort exerted and rewards obtained interact in shaping the behavior in a modified dictator game. We find that dictators condition their choices on recipients' expectations only when there is a high probability that the the recipient will not be compensated for her effort. Otherwise, dictators tend to balance the efforts and rewards of the recipients, irrespective of the recipients' expectations. In the second chapter, I investigate the problem of local opposition to large public projects (e.g. landfills, incinerators, etc.). In particular, the experiment shows how the uncertainty about the project's quality makes the community living in the host site skeptical about the project. I also test whether side-transfers and costly information disclosure can help to increase the efficiency. Both tools succesfully make the host more willing to accept the project, but they lead to the realization of different types of projects. The last chapter is an experiment on climate negotiations. To avoid the global warming, countries are called to cooperate in the abatement of their emissions. We study whether the dynamic aspect of the climate change makes cooperation across countries behaviorally more difficult. We also consider inequality across countries as a possible factor that hinders international cooperation.