Rapporti tra tettonica e clima durante l'esumazione nelle Alpi Centrali. Evidenze dalla termocronologia e dall'analisi strutturale lungo il traforo ferroviario del Sempione

(U-Th)/He and fission-track analyses of apatite along deep-seated tunnels crossing high-relief mountain ranges offer the opportunity to investigate climate and tectonic forcing on the topographic evolution. In this study, the thermochronologic analysis of a large set of samples collected in the Simplon railway tunnel (western-central Alps; Italy and Switzerland) and along its surface trace, coupled with kinematic and structural analysis of major fault zones intersecting the tunnel, constrains the phenomena controlling the topographic and structural evolution, during the latest stage of exhumation of the Simplon Massif, and the timing in which they operated. The study area is located at the western margin of the Lepontine metamorphic dome where a complex nappe-stack pertaining to the Penninic and Ultrahelvetic domains experienced a fast exhumation from the latest Oligocene onward. The exhumation was mainly accommodated by a west-dipping low-angle detachment (the Simplon Fault Zone) which is located just 8 km to the west of the tunnel. However, along the section itself several faults related to two principal phases both with important dip-slip kinematics have been detected. Cooling rates derived from our thermocronological data vary from about 10 °C/Ma at about 10 Ma to about 35 °C/Ma in the last 5 Ma. Such increase in the cooling rate corresponds to the most important climatic change recorded in the northern hemisphere in the last 10 Ma, i.e. the shift to wetter conditions at the end of the Messinian salinity crisis and the inception of glacial cycles in the northern hemisphere. In addition, (U-Th)/He and fission-track age patterns lack of important correlation with the topography suggesting that the present-day relief morphology is the result of recent erosional dynamics. More in details, the (U-Th)/He tunnel ages show an impressive uniformity at 2 Ma, whereas cooling rates calculated at 1 Ma increase towards the two major valleys. This indicates a focusing of erosive processes in the valleys which led to the shaping of present-day topography. Structural analysis documents the presence of two phases of brittle deformation postdating the metamorphic phases in the area. The first one is directly related to the last phase of activity along the Simplon Fault Zone and is characterized by extension towards SO and vertical shortening. The young one is characterized by extension towards NO and horizontal shortening in a along the NE-SO direction. Structures related to the first phase of brittle deformation generate important variations in the older ages' dataset, until 3 Ma, suggesting that tectonics controlled rocks exhumation up to that age. Structures related to the second phase generate some variations also in the younger age dataset, highlighting the activity of faults bordering the massif and suggesting a continuous activity also after 2 Ma. However, most of (U-Th)/He tunnel ages, varying slightly around 2 Ma, document that the Simplon area has experienced primarily erosional exhumation in this time span. In conclusion, all our data suggest that in the central Italian Alps the climatic signal gradually overrode the tectonic effects after about 5 Ma, as a consequence of the climatic instability started at end of Messinian salinity crisis and improved by the onset of glaciations in the northern hemisphere.

Trasduzione del segnale e poliamine nell'apoptosi di cellule cardiache

Introduction: Apoptotic cell death of cardiomyocytes is involved in several cardiovascular diseases including ischemia, hypertrophy and heart failure, thus representing a potential therapeutic target. Apoptosis of cardiac cells can be induced experimentally by several stimuli including hypoxia, serum withdrawal or combination of both. Several lines of research suggest that neurohormonal mechanisms play a central role in the progression of heart failure. In particular, excessive activation of the sympathetic nervous system or the renin-angiotensin-aldosterone system is known to have deleterious effects on the heart. Recent studies report that norepinephrine (NE), the primary transmitter of sympathetic nervous system, and aldosterone (ALD), which is actively produced in failing human heart, are able to induce apoptosis of rat cardiomyocytes. Polyamines are biogenic amines involved in many cellular processes, including apoptosis. Actually it appears that these molecules can act as promoting, modulating or protective agents in apoptosis depending on apoptotic stimulus and cellular model. We have studied the involvement of polyamines in the apoptosis of cardiac cells induced in a model of simulated ischemia and following treatment with NE or ALD. Methods: H9c2 cardiomyoblasts were exposed to a condition of simulated ischemia, consisting of hypoxia plus serum deprivation. Cardiomyocyte cultures were prepared from 1-3 day-old neonatal Wistar rat hearts. Polyamine depletion was obtained by culturing the cells in the presence of α-difluoromethylornithine (DFMO). Polyamines were separated and quantified in acidic cellular extracts by HPLC after derivatization with dansyl chloride. Caspase activity was measured by the cleavage of the fluorogenic peptide substrate. Ornithine decarboxylase (ODC) activity was measured by estimation of the release of 14C-CO2 from 14C-ornithine. DNA fragmentation was visualized by the method of terminal transferase-mediated dUTP nick end-labeling (TUNEL), and DNA laddering on agarose gel electophoresis. Cytochrome c was detected by immunoflorescent staining. Activation of signal transduction pathways was investigated by western blotting. Results: The results indicate that simulated ischemia, NE and ALD cause an early induction of the activity of ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, followed by a later increase of caspase activity, a family of proteases that execute the death program and induce cell death. This effect was prevented in the presence of DFMO, an irreversible inhibitor of ODC, thus suggesting that polyamines are involved in the execution of the death program activated by these stimuli. In H9c2 cells DFMO inhibits several molecular events related to apoptosis that follow simulated ischemia, such as the release of cytochrome c from mitochondria, down-regulation of Bcl-xL, and DNA fragmentation. The anti-apoptotic protein survivin is down-regulated after ALD or NE treatement and polyamine depletion obtained by DFMO partially opposes survivin decrease. Moreover, a study of key signal transduction pathways governing cell death and survival, revealed an involvement of AMP activated protein kinase (AMPK) and AKT kinase, in the modulation by polyamines of the response of cardiomyocytes to NE. In fact polyamine depleted cells show an altered pattern of AMPK and AKT activation that may contrast apoptosis and appears to result from a differential effect on the specific phosphatases that dephosphorylate and switch off these signaling proteins. Conclusions: These results indicate that polyamines are involved in the execution of the death program activated in cardiac cells by heart failure-related stimuli, like ischemia, ALD and NE, and suggest that their apoptosis facilitating action is mediated by a network of specific phosphatases and kinases.

Soil-structure interaction during tunnelling in urban area: observations and 3D numerical modelling

This work illustrates a soil-tunnel-structure interaction study performed by an integrated,geotechnical and structural,approach based on 3D finite element analyses and validated against experimental observations.The study aims at analysing the response of reinforced concrete framed buildings on discrete foundations in interaction with metro lines.It refers to the case of the twin tunnels of the Milan (Italy) metro line 5,recently built in coarse grained materials using EPB machines,for which subsidence measurements collected along ground and building sections during tunnelling were available.Settlements measured under freefield conditions are firstly back interpreted using Gaussian empirical predictions. Then,the in situ measurements’ analysis is extended to include the evolving response of a 9 storey reinforced concrete building while being undercrossed by the metro line.In the finite element study,the soil mechanical behaviour is described using an advanced constitutive model. This latter,when combined with a proper simulation of the excavation process, proves to realistically reproduce the subsidence profiles under free field conditions and to capture the interaction phenomena occurring between the twin tunnels during the excavation. Furthermore, when the numerical model is extended to include the building, schematised in a detailed manner, the results are in good agreement with the monitoring data for different stages of the twin tunnelling. Thus, they indirectly confirm the satisfactory performance of the adopted numerical approach which also allows a direct evaluation of the structural response as an outcome of the analysis. Further analyses are also carried out modelling the building with different levels of detail. The results highlight that, in this case, the simplified approach based on the equivalent plate schematisation is inadequate to capture the real tunnelling induced displacement field. The overall behaviour of the system proves to be mainly influenced by the buried portion of the building which plays an essential role in the interaction mechanism, due to its high stiffness.