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The structure of a volcanic edifice depends on composition, volume of erupted magma, and mechanism of eruption. In particular, pressure variations with depth due to density variations of the volcanic rocks are crucial for magma degassing processes as well as buoyancy mechanisms. In this paper, we analyze the effects of three different pressure profiles with depth on the probability of occurrence of simulated eruptive events. We describe the dynamics of magma ascent by means of a time dependent Self-Organized-Criticality field, which controls the opening of crack networks through which discrete magma batches are allowed to rise. We find a characteristic power-law behavior for the number of eruptions with erupted volume in all considered cases. As concerns the probability of occurrence of an eruptive event with a given percentage of gas losses, we find that extreme events, i.e., events with the lowest percentage of gas losses, are more likely to occur if a step function is used to describe the relationship between rock density and depth.

Landslide inventories show that the statistical distribution of the area of recorded events is well described by a power law over a range of decades. To understand these distributions, we consider a cellular automaton to model a time and position dependent factor of safety. The model is able to reproduce the complex structure of landslide distribution, as experimentally reported. In particular, we investigate the role of the rate of change of the system dynamical variables, induced by an external drive, on landslide modeling and its implications on hazard assessment. As the rate is increased, the model has a crossover from a critical regime with power-laws to non power-law behaviors. We suggest that the detection of patterns of correlated domains in monitored regions can be crucial to identify the response of the system to perturbations, i.e., for hazard assessment., Comment: 4 pages, 3 figures

1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. 2. We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. 3. Bronchial tissues after endothelin treatment were exposed to a standard electrical field stimulation (EFS) (30% of EFS 30 Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK(2) receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath fluid samples. Moreover, the human bronchi were used for the beta-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT - PCR), prior to and 30-40 min following ET-1 challenge. 4. The selective tachykinin NK(2) receptor antagonist, SR48968, was effective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed significant increased quantities of NKA in organ bath effluents after EFS stimulation in bronchi pretreated with ET-1. Finally, beta-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. 5. In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production.

[1] Understanding the mechanisms of magma ascent preceding eruptions, and in particular the subvolcanic system that stores and transports magma to the surface, is of crucial relevance for hazard and risk assessment. We propose here a statistical model describing the rise of magma from the reservoir through the transport region via stress induced fracturing mechanisms of the medium. The model reproduces the general statistical properties of erupted volume, P( V), and inter-eruption time, P(t), found in catalogue data for closed conduit volcanoes. We also investigate conditional distribution ( e. g., the probability, P( V vertical bar t), to have a volume, V, erupted after a waiting time, t), which can have important practical implications.

Abstract An integrated approach that combines geophysical surveys and numerical simulations is proposed to study the processes that govern the fluid flow along active fault zones. It is based on the reconstruction of the architecture of the investigated fault system, as well as the identification of possible paths for fluid migration, according to the distribution of geophysical parameters retrieved by multi-methodological geophysical prospecting. The aim is to establish, thanks to constraints deriving from different types of data (e.g., geological, geochemical and/or hydrogeological data), an accurate 3D petrophysical model of the survey area to be used for simulating, by numerical modelling, the physical processes likely taking place in the imaged system and its temporal evolution. The effectiveness of the proposed approach is tested in an active fault zone in the Matese Mts (southern Italy), where recent, accurate geochemical measurements have registered very high anomalous values of non-volcanic natural emissions of CO2. In particular, a multi-methodological geophysical survey, consisting of electrical resistivity tomography, self-potential and passive seismic measurements, integrated with geological data, was chosen to define the 3D petrophysical model of the investigated system and to identify possible source geometries. Three different scenarios were assumed corresponding to three different CO2 source models. The one that hypothesizes a source located along the fault plane at the depth of the carbonate basement was found to be the best candidate to represent the test site. Indeed, the performed numerical simulations provide CO2 flow estimates comparable with the values observed in the investigated area. These findings are promising for gas hazards, as they suggest that numerical simulations of different CO2 degassing scenarios could forecast possible critical variations in the amount of CO2 emitted near the fault.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pulmonary emphysema is a respiratory condition characterized by alveolar destruction that leads to airflow limitation and reduced lung function. Although with extensive research, the pathophysiology of emphysema is poorly understood and effective treatments are still missing. Evidence suggests that mesenchymal stem cells (MSCs) possess the ability to engraft the injured tissues and induce repair via a paracrine effect. Thus, the aim of this study was to test the effects of the intratracheal administration of lung-derived mouse MSCs in a model of elastase-induced emphysema. Pulmonary function (static lung compliance) showed an increased stiffness induced by elastase, while morphometric findings (mean linear intercept and tissue/alveolar area) confirmed the severity of alveolar disruption. Contrarily, MSC administration partially restored lung elasticity and alveolar architecture. In the absence of evidence that MSCs acquired epithelial phenotype, we detected an increased proliferative activity of aquaporin 5-and surfactant protein C-positive lung cells, suggesting MSC-driven paracrine mechanisms. The data indicate the mediation of hepatocyte growth factor in amplifying MSC-driven tissue response after injury. Our study shed light on supportive properties of lung-derived MSCs, although the full identification of mechanisms orchestrated by MSCs and responsible for epithelial repair after injury is a critical aspect yet to be achieved. Copyright © 2018 Donato Cappetta et al. Pulmonary emphysema is a respiratory condition characterized by alveolar destruction that leads to airflow limitation and reduced lung function. Although with extensive research, the pathophysiology of emphysema is poorly understood and effective treatments are still missing. Evidence suggests that mesenchymal stem cells (MSCs) possess the ability to engraft the injured tissues and induce repair via a paracrine effect. Thus, the aim of this study was to test the effects of the intratracheal administration of lung-derived mouse MSCs in a model of elastase-induced emphysema. Pulmonary function (static lung compliance) showed an increased stiffness induced by elastase, while morphometric findings (mean linear intercept and tissue/alveolar area) confirmed the severity of alveolar disruption. Contrarily, MSC administration partially restored lung elasticity and alveolar architecture. In the absence of evidence that MSCs acquired epithelial phenotype, we detected an increased proliferative activity of aquaporin 5- and surfactant protein C-positive lung cells, suggesting MSC-driven paracrine mechanisms. The data indicate the mediation of hepatocyte growth factor in amplifying MSC-driven tissue response after injury. Our study shed light on supportive properties of lung-derived MSCs, although the full identification of mechanisms orchestrated by MSCs and responsible for epithelial repair after injury is a critical aspect yet to be achieved.

Cardiotoxicity remains a serious problem in anthracycline-treated oncologic patients. Therapeutic modulation of microRNA expression is emerging as a cardioprotective approach in several cardiovascular pathologies. MiR-34a increased in animals and patients exposed to anthracyclines and is involved in cardiac repair. In our previous study, we demonstrated beneficial effects of miR-34a silencing in rat cardiac cells exposed to doxorubicin (DOXO). The aim of the present work is to evaluate the potential cardioprotective properties of a specific antimiR-34a (Ant34a) in an experimental model of DOXO-induced cardiotoxicity. Results indicate that in our model systemic administration of Ant34a completely silences miR-34a myocardial expression and importantly attenuates DOXO-induced cardiac dysfunction. Ant34a systemic delivery in DOXO-treated rats triggers an upregulation of prosurvival miR-34a targets Bcl-2 and SIRT1 that mediate a reduction of DOXO-induced cardiac damage represented by myocardial apoptosis, senescence, fibrosis and inflammation. These findings suggest that miR-34a therapeutic inhibition may have clinical relevance to attenuate DOXO-induced toxicity in the heart of oncologic patients.

The magnetotelluric (MT) method is useful for monitoring geophysical processes because of a large dynamic depth range. In this paper, a feasibility study of employing continuous MT observations to monitor hydrothermal systems for both volcanic hazard assessment and geothermal energy exploitation is presented. Sensitivity of the MT method has been studied by simulating spatial and temporal evolution of temperature and gas saturation distributions in a hydrothermal system, and by calculating the MT response at different time steps. Two possible scenarios have been considered: the first is related to an increase in the fluid flow rate at the system source, the second is associated to an increase in the permeability of the rocks hosting the hydrothermal system. Numerical simulations have been performed for each scenario, and the sensitivity of the MT monitoring has been analyzed by evaluating the time interval needed to observe significant variations in the MT response. This study has been applied to the hydrothermal system of the Campi Flegrei (southern Italy) and it has shown that continuous MT measurements are not sensitive enough to detect a significant increase in the source fluid flow rate over time intervals less than ten years. On the contrary, if the permeability of the upwelling zone increases, a measurable change in the MT response occurs over a time interval ranging from six months to three years, depending on the extent of the permeability increase. Such findings are promising and suggest that continuous MT observations in active volcanic areas can be useful for imaging volcano-hydrothermal system activity.

Background Doxorubicin (DOXO) is an effective anti-neoplastic drug but its clinical benefits are hampered by cardiotoxicity. Oxidative stress, apoptosis and myocardial fibrosis mediate the anthracycline cardiomyopathy. ROS trigger TGF-β pathway that activates cardiac fibroblasts promoting fibrosis. Myocardial stiffness contributes to diastolic dysfunction, less studied aspect of anthracycline cardiomyopathy. Considering the role of SIRT1 in the inhibition of the TGF-β/SMAD3 pathway, resveratrol (RES), a SIRT1 activator, might improve cardiac function by interfering with the development of cardiac fibrosis in a model of DOXO-induced cardiomyopathy. Methods F344 rats received a cumulative dose of 15 mg/kg of DOXO in 2 weeks or DOXO + RES (DOXO and RES, 2.5 mg/kg/day, concomitantly for 2 weeks and then RES alone for 1 more week). The effects of RES on cardiac fibroblasts were also tested in vitro. Results Along with systolic dysfunction, DOXO was also responsible of diastolic abnormalities. Myocardial stiffness correlated with fibroblast activation and collagen deposition. DOXO + RES co-treatment significantly improved ± dP/dt and, more interestingly, ameliorated end-diastolic pressure/volume relationship. Treatment with RES resulted in reduced fibrosis and fibroblast activation and, most importantly, the mortality rate was significantly reduced in DOXO + RES group. Fibroblasts isolated from DOXO + RES-treated rats, in which SIRT1 was upregulated, showed decreased levels of TGF-β and pSMAD3/SMAD3 when compared to cells isolated from DOXO-exposed hearts. Conclusions Our findings reveal a key role of SIRT1 in supporting animal survival and functional parameters of the heart. SIRT1 activation by interfering with fibrogenesis can improve relaxation properties of myocardium and attenuate myocardial remodeling related to chemotherapy. © 2015 Elsevier Ireland Ltd. All rights reserved

The thermal evolution of the Phlegraean magmatic system (southern Italy) is studied by analyzing the influence of the thermal property variations on the solution of the heat conduction equation. The aim of this paper is to verify if appropriate choices of thermal parameters can reproduce, at least to greater depths, the high temperatures measured in the geothermal wells, drilled inside the caldera, under the assumption of heat loss from a magma chamber by conduction. Since the main purpose is to verify the plausibility of such an assumption, rather simple models of the magmatic system are adopted and only major volcanic events (i.e., the Campanian Ignimbrite and the Neapolitan Yellow Tuff eruptions) are considered. The results of the simulated two-dimensional model scenarios show that by assuming an extended source region, whose emplacement time is longer than 40 ka, heat conduction mechanisms can provide temperatures as high as those measured at depths deeper than about 2000 m. On the other hand, the 1D simulations show that appropriate choices for the thermal conductivity depth profiles can reproduce the observed temperatures at depths deeper than about 1000 m. These findings question the apparent consensus that convection is the only dominant form of heat transfer at Phlegraean Fields and might motivate new research for reconstructing the thermal evolution of the Phlegraean magmatic system.

We simulated the pattern of activity of a strato-volcano by using a cellular automaton model where magma is allowed to ascend to the surface through self-organized crack networks. Magma rises toward the surface by filling connected paths of fractures until the magma's density is less than that of surrounding rocks. If magma enters a region with negative or neutral buoyancy, it cools and solidifies; as a result, the local density profile is modified, and magmatic dikes are formed. We simulated the temporal evolution of high-density pathways of dikes that magma may eventually utilize to reach the surface. We showed that if a shallow neutral–negative buoyancy zone is restored after eruptions, due to, for example, piecemeal or chaotic collapses, a characteristic timescale appears in the inter-event repose time distribution. Such characteristic repose time represents the average time that magma takes to form a high-density pathway through the less dense rock layer, and it may give a hint to predict possible eruptive scenarios. Even if the model includes many simplifying assumptions in the definition of magma–rock interaction, the results obtained from simulations are consistent with the eruptive behavior of the Mt. Somma-Vesuvius volcano for the 1631–1944 period.

Volcanoes are complex dynamical systems that manifest their activity in a wide range of eruptions with different explosivity. In this paper, we propose a cellular automaton model aimed at capturing the key features of the magma ascent dynamics that reproduces the great variability of volcanic explosivity. The novelty of our approach consists in considering an eruption not as an event caused by overpressure in the magma chamber but as the result of transport of discrete magma batches from the reservoir to the surface along preformed crack networks. Since gas is lost during the ascent, the time for the rise of magma is crucial. In our model, such a time is related to the opening of connected paths of fractures in the surrounding rocks, which are described by means of a time dependent Self-Organized-Criticality field. We analyze statistical distributions of eruptions in terms of gas losses and find that eruptions with the lowest degree of explosiveness are characterized by small erupted volumes, even if they are much more likely to occur than explosive eruptions. On the contrary, explosive eruptions, which in our model essentially correspond to percolative events that directly connect the magma reservoir to the surface, are rare events that can be very huge.

Landslides are natural hazards occurring in response to triggers of different origins, which can act with different intensities and durations. Despite the variety of conditions that cause a landslide, the analysis of landslide inventories has shown that landslide events associated with different triggers can be characterized by the same probability distribution. We studied a cellular automaton, able to reproduce the landslide frequency-size distributions from catalogues. From the comparison between our synthetic probability distribution and the landslide area probability distribution of three landslide inventories, we estimated the typical size of a single cell of our cellular automaton model to be from 35–100 m2, which is important information if we are interested in monitoring a test area. To determine the probability of occurrence of a landslide of size s, we show that it is crucial to get information about the rate at which the system is approaching instability rather than the nature of the trigger. By varying such a driving rate, we find how the probability distribution changes and, in correspondence, how the size and the lifetime of the most probable events evolve. We also introduce a landslide-event magnitude scale based on the driving rate. Large values of the proposed intensity scale are related to landslide events with a fast approach to instability in a long distance of time, while small values are related to landslide events close together in time and approaching instability slowly.

Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit+ cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit+ cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit+ cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit+ cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGFβ were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit+ cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit+ cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit+ cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.

// Elena Piegari 1, * , Rosa Russo 1, * , Donato Cappetta 1 , Grazia Esposito 1 , Konrad Urbanek 1 , Carmela Dell’Aversana 2 , Lucia Altucci 2, 3 , Liberato Berrino 1 , Francesco Rossi 1 , Antonella De Angelis 1 1 Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy 2 Institute of Genetics and Biophysics, IGB ‘Adriano Buzzati-Traverso’, Naples, Italy 3 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy * These authors have contributed equally to this work Correspondence to: Elena Piegari, email: elena.piegari@unina2.it Keywords: miR-34a, doxorubicin-induced cardiotoxicity, rat cardiac progenitor cells, SIRT1, cellular senescence Received: February 03, 2016 Accepted: July 26, 2016 Published: August 22, 2016 ABSTRACT New strategies to prevent and early detect the cardiotoxic effects of the anticancer drug doxorubicin (DOXO) are required. MicroRNAs emerged as potential diagnostic, therapeutic and prognostic approaches in cardiovascular diseases. MiR-34a has a role in cardiac dysfunction and ageing and is involved in several cellular processes associated with DOXO cardiotoxicity. Our in vitro and in vivo results indicated that after DOXO exposure the levels of miR-34a are enhanced in cardiac cells, including Cardiac Progenitor Cells (CPCs). Since one of the determining event responsible for the initiation and evolution of the DOXO toxicity arises at the level of the CPC compartment, we evaluated if miR-34a pharmacological inhibition in these cells ameliorates the detrimental aftermath of the drug. AntimiR-34a has beneficial consequences on vitality, proliferation, apoptosis and senescence of DOXO-treated rat CPC. These effects are mediated by an increase of prosurvival miR-34a targets Bcl-2 and SIRT1, accompanied by a decrease of acetylated-p53 and p16 INK4a . Importantly, miR-34a silencing also reduces the release of this miRNA from DOXO-exposed rCPCs, decreasing its negative paracrine effects on other rat cardiac cells. In conclusion, the silencing of miR-34a could represent a future therapeutic option for cardioprotection in DOXO toxicity and at the same time, it could be considered as a circulating biomarker for anthracycline-induced cardiac damage.

Background: The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce. Objectives: To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model. Methods: GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro. Results: Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties. Conclusion: Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue remodeling. © 2016 Urbanek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Although low-energy extracorporeal cardiac shock wave (ECSW) therapy represents an attractive non-invasive treatment option for ischaemic heart disease, the precise mechanisms of its action and influence on the cardiac tissue remain obscure. The goal of this study was to evaluate the effects of SW application on cardiac function and structure. Four-month-old Fisher 344 rats were subjected to ECSW therapy. Echocardiographic measurements of cardiac function were performed at baseline and at 1 and 3 months after treatment. Signs of inflammation, apoptosis and fibrosis were evaluated by immunohistochemistry in the control and treated hearts. ECSW application did not provoke arrhythmia or increase the troponin-I level. At all time points, the left ventricular ejection fraction and fractional shortening remained stable. Histological analysis revealed neither differences in the extracellular matrix collagen content nor the presence of fibrosis; similarly, there were no signs of inflammation. Moreover, a population of cardiac cells that responded eagerly to ECSW application in the adult heart was identified; c-kit–positive, Ki67-positive, orthochromatic cells, corresponding to cardiac primitive cells, were 2.65-fold more numerous in the treated myocardium. In conclusion, non-invasive ECSW therapy is a safe and effective way of activating cardiac stem cells and myocardial regeneration. Because many factors influence cellular turnover in the ischaemic myocardium during the course of ischaemic heart disease, cardiac remodelling, and heart failure progression, studies to identify the optimal treatment time are warranted.

Background— Anthracyclines are the most effective drugs available in the treatment of neoplastic diseases; however, they have profound consequences on the structure and function of the heart, which over time cause a cardiomyopathy that leads to congestive heart failure. Methods and Results— Administration of doxorubicin in rats led to a dilated myopathy, heart failure, and death. To test whether the effects of doxorubicin on cardiac anatomy and function were mediated by alterations in cardiac progenitor cells (CPCs), these cells were exposed to the anthracycline, which increased the formation of reactive oxygen species and caused increases in DNA damage, expression of p53, telomere attrition, and apoptosis. Additionally, doxorubicin resulted in cell-cycle arrest at the G2/M transition, which led to a significant decrease in CPC growth. Doxorubicin elicited multiple molecular adaptations; the massive apoptotic death that occurred in CPCs in the presence of anthracycline imposed on the surviving CPC pool the activation of several pathways aimed at preservation of the primitive state, cell division, lineage differentiation, and repair of damaged DNA. To establish whether delivery of syngeneic progenitor cells opposed the progression of doxorubicin cardiotoxicity, enhanced green fluorescent protein–labeled CPCs were injected in the failing myocardium; this treatment promoted regeneration of cardiomyocytes and vascular structures, which improved ventricular performance and rate of animal survival. Conclusions— Our results raise the possibility that autologous CPCs can be obtained before antineoplastic drugs are given to cancer patients and subsequently administered to individuals who are particularly sensitive to the cardiotoxicity of these agents for prevention or management of heart failure.

In order to characterize landslide frequency-size distributions and individuate hazard scenarios and their possible precursors, we investigate a cellular automaton where the effects of a finite driving rate and the anisotropy are taken into account. The model is able to reproduce observed features of landslide events, such as power-law distributions, as experimentally reported. We analyze the key role of the driving rate and show that, as it is increased, a crossover from power-law to non power-law behaviors occurs. Finally, a systematic investigation of the model on varying its anisotropy factors is performed and the full diagram of its dynamical behaviors is presented., Comment: 8 pages, 9 figures