Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1-dependent mechanism

In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells. DNA demethylation is mediated by ten-eleven translocation enzymes (TETs). They sequentially convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is associated with active transcription; 5-formylcytosine; and finally, 5-carboxylcytosine. Although α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid, the major n-3 polyunsaturated fatty acids, have anti-cancer effects, their action, as DNA-demethylating agents, has never been investigated in solid tumor cells. Here, we report that EPA demethylates DNA in hepatocarcinoma cells. EPA rapidly increases 5hmC on DNA, inducing p21Waf1/Cip1 gene expression, which slows cancer cell-cycle progression. We show that the underlying molecular mechanism involves TET1. EPA simultaneously binds peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα), thus promoting their heterodimer and inducing a PPARγ-TET1 interaction. They generate a TET1-PPARγ-RXRα protein complex, which binds to a hypermethylated CpG island on the p21 gene, where TET1 converts 5mC to 5hmC. In an apparent shuttling motion, PPARγ and RXRα leave the DNA, whereas TET1 associates stably. Overall, EPA directly regulates DNA methylation levels, permitting TET1 to exert its anti-tumoral function.-Ceccarelli, V., Valentini, V., Ronchetti, S., Cannarile, L., Billi, M., Riccardi, C., Ottini, L., Talesa, V. N., Grignani, F., Vecchini, A., Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1-dependent mechanism

MONITORING AND CHARACTERIZATION OF A SPRING IN A FRACTURED SANDSTONE SLAB

Fractured sandstone by tectonic and gravity actions could be classified as aquitard or aquifer according to the number and aperture of the fractures inside the rock mass. This kind of rock mass outcrops not frequently and sparsely in the Apennine and Alps chains. In the Emilian Apennines, which is mainly composed by sedimentary rocks (rich in clay), this type of rock is part of the Epiligurian Succession that outcrops for a 20 percent of the chain. The paper aims to highlight the first results of the semi-continuous water flow monitoring (discharge, electrical conductivity and temperature) and stable isotopic monitoring (delta18O and delta2H) of the spring that represents the drainage point of a vertical fractures system. This network joint characterizes the vertical scarp of a sandstone slab with thickness of 100 meters. The results show that the spring flow rate, the water electrical conductivity, temperature and isotopic values are influenced by the rainfall distribution pattern. Consequently during every rainfall event the spring discharge and water electrical conductivity increase, while the water temperature decreases and isotopic values become more negative. The new infiltrate water reachs the spring with a delay of 10-60 hours. The discharge variability index is around 270 percent. The fractured system is characterized by replacement effect of the preexistent groundwater. During the infiltration event, dissolution phenomena are observed along the wall of the fractures. A preliminary groundwater budget calculation highlights that only a potential infiltration coefficient higher that 75 percent is admitted to justify the total annual volume discharge from the fractures

Estimating the Isotopic Altitude Gradient for Hydrogeological Studies in Mountainous Areas: Are the Low-Yield Springs Suitable? Insights from the Northern Apennines of Italy

Several prior studies investigated the use of stable isotopes of water in hydrogeological applications, most on a local scale and often involving the isotopic gradient (evaluated by exploiting the so-called altitude effect), calculated on the basis of rainwater isotopes. A few times, this gradient has been obtained using the stable isotopic contents of low-yield springs in a limited time series. Despite the fact that this method has been recognized by the hydrogeological community, marked differences have been observed with respect to the mean stable isotopes content of groundwater and rainwater. The present investigation compares the stable isotopic signatures of 23 low-yield springs discharging along two transects from the Tyrrhenian sea to the Po Plain of Italy, evaluates the different isotopic gradients and assesses their distribution in relation to some climatic and topographic conditions. Stable isotopes of water show that groundwater in the study area is recharged by precipitation and that the precipitation regime in the eastern portion of the study area is strongly controlled by a shadow effect caused by the Alps chain on the air masses from central Europe. Stable isotopes (in particular the d18O and deuterium excess (d-excess) contents together with the obtained isotopic gradients) allow us to identify in the study area an opposite oriented orographic effect and a different provenance of the air masses. When the windward slope is located on the Tyrrhenian side, the precipitation shows a predominant oceanic origin; when the windward slope moves to the Adriatic side, the precipitation is characterized by a continental origin. The main results of this study confirm the usefulness of low-yield springs and the need for a highly detailed survey-scale hydrological investigation in the mountainous context

Integrated Surveying System for Landslide Monitoring, Valoria Landslide (Appennines of Modena, Italy)

The research object is the study and prevention of landslide risk through the utilization of integrated surveying systems like GPS and Automatic Total Station (Robotic station).The measurements have been applied to Boschi di Valoria landslide, located on Appennines of Modena in the Northern Italy, which relatively large size, about 1.6 square km, required the use of both techniques. The system is made by Automatic Total Station, looking at 45 reflectors and a GPS master station, reference for three rovers on the landslide. In order to monitor "local" disturbing effects, a bi-dimensional clinometer has been applied on the pilaster where the total station is located. In a first periodically measurements were collected, while the system is now performing continuously. The system permitted to evaluate movements from few millimeter till some meters per day in most dangerous areas; the entity of the movements obliged to plan an alert system that was activated after a first phase of phenomenon study. Topographic measurements have been integrated with geotechnical sensors (inclinometers and piezometers) in a GIS for landslide risk management

Groundwater processes in a complex landslide, northern Apennines, Italy

The hydrogeological characteristics of rototranslationalslides in flysch are complex, due to the inherentanisotropy and heterogeneity of rock masses and related deposits.The paper deals with the hydrogeological characterizationof a reactivated roto-translational slide affecting Cretaceousflysch rocks, located in the northern Apennines ofItaly. Continuous monitoring of groundwater levels, in-situpermeability and pumping tests, hydrochemical and physicalanalyses and Uranine tracers were the adopted prospectingmethods.In this research hydrological monitoring and investigationare summarized in order to define a hydrogeological conceptualmodel of the landslide source area. Results showed thattwo overlaying hydrogeological units exist at the slope scale:the first is unconfined, but highly compartmentalized, andhosted in the fractured and dismembered rock slide body.The second is confined and lays in the undisturbed flyschbelow the sliding surface. The groundwater level in theconfined hydrogeological unit is twenty meters higher thanthe groundwater level in the uppermost one. Moreover, thegroundwater chemistry characterization revealed a rising ofdeep fluids in the landslide area

Stochastic approach to hydraulic barrier design: an example in northeastern Italy

Volatile organic compounds, groundwater contamination, multi-layered aquifer syste

Toward a centralized data management center for integrated landslide monitoring in Emilia Romagna Region (Italy)

In Emilia Romagna Region, slope monitoring systems have become more widely used for hazard and risk management. However, they are generally non-interoperable. Moreover dispersion of monitoring data in several local databases have made data sharing among the involved institutional actors quite laborious and often untimely. A centralized database and a web-based portal that integrate infor- mation derived by different types of slope monitoring systems has been developed. The paper illustrates the specific features of the developed “SensorNet” and provides examples of its use for visualizing and analyzing in an integrated manner data from different monitoring systems. In perspective it could serve as an every-day operational tool for a timely reporting of landslide monitoring data for surveillance and warning purposes