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MicroRNA-1 Downregulation Increases Connexin 43 Displacement and Induces Ventricular Tachyarrhythmias in Rodent Hypertrophic Hearts
Antonio Curcio, Daniele Torella, Claudio Iaconetti, Eugenia Pasceri, Jolanda Sabatino, Sabato Sorrentino, Salvatore Giampà, Mariella Micieli, Alberto Polimeni, Beverley J. Henning, Angelo Leone, Daniele Catalucci, Georgina M. Ellison, Gianluigi Condorelli, Ciro Indolfi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070158
Abstract: Downregulation of the muscle-specific microRNA-1 (miR-1) mediates the induction of pathologic cardiac hypertrophy. Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT). However, it is still unknown whether miR-1 and Cx43 are interconnected in the pro-arrhythmic context of hypertrophy. Thus, in this study we investigated whether a reduction in the extent of cardiac hypertrophy could limit the pathological electrical remodeling of Cx43 and the onset of VT by modulating miR-1 levels. Wistar male rats underwent mechanical constriction of the ascending aorta to induce pathologic left ventricular hypertrophy (LVH) and afterwards were randomly assigned to receive 10mg/kg valsartan, VAL (LVH+VAL) delivered in the drinking water or placebo (LVH) for 12 weeks. Sham surgery was performed for control groups. Programmed ventricular stimulation reproducibly induced VT in LVH compared to LVH+VAL group. When compared to sham controls, rats from LVH group showed a significant decrease of miR-1 and an increase of Cx43 expression and its ERK1/2-dependent phosphorylation, which displaces Cx43 from the gap junction. Interestingly, VAL administration to rats with aortic banding significantly reduced cardiac hypertrophy and prevented miR-1 down-regulation and Cx43 up-regulation and phosphorylation. Gain- and loss-of-function experiments in neonatal cardiomyocytes (NCMs) in vitro confirmed that Cx43 is a direct target of miR-1. Accordingly, in vitro angiotensin II stimulation reduced miR-1 levels and increased Cx43 expression and phosphorylation compared to un-stimulated NCMs. Finally, in vivo miR-1 cardiac overexpression by an adenoviral vector intra-myocardial injection reduced Cx43 expression and phosphorylation in mice with isoproterenol-induced LVH. In conclusion, miR-1 regulates Cx43 expression and activity in hypertrophic cardiomyocytes in vitro and in vivo. Treatment of pressure overload-induced myocyte hypertrophy reduces the risk of life-threatening VT by normalizing miR-1 expression levels with the consequent stabilization of Cx43 expression and activity within the gap junction.
Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action
Esther Llagostera, Daniele Catalucci, Luc Marti, Marc Liesa, Marta Camps, Theodore P. Ciaraldi, Richard Kondo, Sita Reddy, Wolfgang H. Dillmann, Manuel Palacin, Antonio Zorzano, Pilar Ruiz-Lozano, Ramon Gomis, Perla Kaliman
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0001134
Abstract: Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk?/?) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk?/? mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk?/? mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.
Pediatric Stroke: Clinical Findings and Radiological Approach
Giuseppe Lanni,Alessia Catalucci,Laura Conti,Alessandra Di Sibio,Amalia Paonessa,Massimo Gallucci
Stroke Research and Treatment , 2011, DOI: 10.4061/2011/172168
Abstract: This paper focuses on radiological approach in pediatric stroke including both ischemic stroke (Arterial Ischemic Stroke and Cerebral Sinovenous Thrombosis) and hemorrhagic stroke. Etiopathology and main clinical findings are examined as well. Magnetic Resonance Imaging could be considered as the first-choice diagnostic exam, offering a complete diagnostic set of information both in the discrimination between ischemic/hemorrhagic stroke and in the identification of underlying causes. In addition, Magnetic Resonance vascular techniques supply further information about cerebral arterial and venous circulation. Computed Tomography, for its limits and radiation exposure, should be used only when Magnetic Resonance is not available and on unstable patients. 1. Introduction Pediatric stroke (PS) is a relatively rare disease, having an estimated incidence of 2.5–13/100,000/year [1–4], but remains one of the most common causes of death in childhood, with a mortality rate of 0.6/100,000 dead/year [5, 6]. PS has also seriously high morbidity and long-term outcome and is nowadays gaining more interest because of its heavy consequences and costs, both personal and social. Indeed, about half of the surviving patients develop some neurologic or cognitive impairment, and just more than a quarter, epilepsy. As in adults, PS can be ischemic or hemorrhagic; although ischemic stroke is more common, prevalence is variable [7, 8]. Ischemic stroke includes Arterial Ischemic Stroke (AIS) and Cerebral Sinovenous Thrombosis (CSVT); Hemorrhagic Stroke (HS) includes intracerebral and subarachnoid haemorrhage [9]. AIS, both in neonatal and childhood forms, has a higher incidence among males [5, 10–14] and black people [5, 7]. AIS is relapsing in 6%–37% of little patients [15–19] and the risk appears highest in the first 6 months after the first episode [19, 20]. Risk factors for relapse include vascular abnormalities as first stroke cause [19, 20], and the presence of thrombotic risk factors [20], either isolated or as part of multiple risk factors [20, 21]. CSVT has an incidence of 2.6/100,000 children/year in the neonatal period and of 0.4 and 0.7/100,000 children/year in childhood [22]. The incidence of hemorrhagic stroke (HS) is estimated between 0.7 to 5.1/100,000 children/year [23, 24] and, similar to childhood AIS, is more common in males and blacks [11, 25]. The mean age at diagnosis is 6–10 years [1]. A prompt and precise diagnosis of PS, associated to an effective management of vascular emergencies, is a crucial point to reach a correct therapy and, consequently, a
Pulmonary congenital cystic adenomatoid malformation, type I, presenting as a single cyst of the middle lobe in an adult: case report
Luca Morelli, Irene Piscioli, Stefano Licci, Salvatore Donato, Alessia Catalucci, Franca Del Nonno
Diagnostic Pathology , 2007, DOI: 10.1186/1746-1596-2-17
Abstract: We report a case of type I CCAM presenting as a single, expansive cystic mass in the middle pulmonary lobe in a 38-year-old man, revealed by persistent cough and haemoptysis. Computed tomographic scan showed a single cyst with air fluid level, occupying the lateral segment of the lobe. When the type I CCAM is a single cyst, other cystic pulmonary lesions must be excluded. The intrapulmonary localization and the absence of cartilage in the cyst wall are conclusive findings of CCAM. The pathogenesis, management and differential diagnosis with other lung malformations are discussed along with a review of the literature.The literature data confirm that surgical resection is the treatment of choice in all cases of CCAM and in the cases of cystic pulmonary lesions with uncertain radiological findings, in order to perform a histological examination of the lesion and to prevent infection and the potential neoplastic transformation.The development of the respiratory system begins at 3 weeks of gestation, and aberrations in developmental processes may give rise to a group of structural abnormalities collectively referred to as bronchopulmonary foregut malformations. These lesions include congenital cystic adenomatoid malformations (CCAMs), sequestrations and infantile lobar emphysema. All congenital malformations of the lower respiratory tract are usually diagnosed and managed antenatally, in the newborn period, in infancy or in childhood. In a small number of patients, such malformations may go unrecognized in infancy, childhood and rarely in adulthood [1,2]. In the latter cases late complications, such as recurrent localized pneumonia, abscess formation, spontaneous pneumothorax, haemoptysis, or coincidental discovery on a chest radiograph may lead to the diagnosis. CCAM is a rare congenital pulmonary lesion, with a reported incidence of 1 in 25.000–35.000 pregnancies [3], involving maldevelopment of terminal branches, as a consequence of abnormal embryogenesis during the f
Ten Years of the Central Italy Electromagnetic Network (CIEN) Continuous Monitoring  [PDF]
Cristiano Fidani, Daniele Marcelli
Open Journal of Earthquake Research (OJER) , 2017, DOI: 10.4236/ojer.2017.62004
Abstract: A test is being realised by means of a network of wide band electromagnetic detectors that continuously records the electric components of the electromagnetic field, ranging from a few of Hz to tens of kHz. The network has been operating in central Italy for more than ten years. The recorded signals from this network have been analysed in real time as well as their power spectrum contents. Time/frequency data have been saved for further analysis. The spectral contents have evidenced very distinct power spectrum signatures in ELF band that increase in intensity when strong seismic activity occurs near the stations, for example, at the time of Amatrice (M = 6) and Norcia (M = 6.5) earthquakes in 2016 when ten stations were operative, at the time of the Emilia (M = 6) earthquakes in 2012 when nine stations were operative, and at the time of the L’Aquila (M = 6.3) earthquakes in 2009 when only two stations were operative. Strong signals were also detected during the moderate Ancona (M = 5) earthquake in 2013 and by the recently installed Avigliano Umbro, Città di Castello and Gubbio stations in the Umbria region, during small seismic swarms (2 < M < 4) between 2013 and 2014. CIEN is presently composed of 16 stations and collect data from a multidisciplinary instrumentation.
Monitoring and Identification of the Seismically Isolated “Our Lady of Tears” Shrine in Syracuse  [PDF]
Daniele Losanno, Mariacristina Spizzuoco
Open Journal of Civil Engineering (OJCE) , 2018, DOI: 10.4236/ojce.2018.84028
Abstract: This paper describes the installation and management of the monitoring system of the “Our Lady of Tears Shrine” in Syracuse, whose dome is an imposing r.c. and prestressed r.c. structure of about 22,000 ton that was seismically isolated by flat sliding devices with hysteretic dampers. The monitoring system, representing an upgrading and improvement of an old system never made working, has some innovative features, because it allows to manage with the same dedicated hardware and software both the slow (thermal variations, relative humidity, wind direction and velocity) and the fast acquisitions (dynamic vibrations by wind and earthquake). The monitoring system was inserted among those structures maintained and controlled by the Seismic Observatory of Structures of the National Department of Civil Protection. Some records of low magnitude earthquakes allowed to validate the correct behaviour of the whole structure, as well as to make a dynamic identification of the complex construction and to calibrate a detailed finite element model of the Sanctuary, thus predicting isolators’ behaviour under design earthquake.
Self gravitating cosmic strings and the Alexandrov's inequality for Liouville-type equations
Daniele Bartolucci,Daniele Castorina
Mathematics , 2014,
Abstract: Motivated by the study of self gravitating cosmic strings, we pursue the well known method by C. Bandle to obtain a weak version of the classical Alexandrov's isoperimetric inequality. In fact we derive some quantitative estimates for weak subsolutions of a Liouville-type equation with conical singularities. Actually we succeed in generalizing previously known results, including Bol's inequality and pointwise estimates, to the case where the solutions solve the equation just in the sense of distributions. Next, we derive some \uv{new} pointwise estimates suitable to be applied to a class of singular cosmic string equations. Finally, interestingly enough, we apply these results to establish a minimal mass property for solutions of the cosmic string equation which are \uv{supersolutions} of the singular Liouville-type equation.
A global existence result for a Keller-Segel type system with supercritical initial data
Daniele Bartolucci,Daniele Castorina
Mathematics , 2015,
Abstract: We consider a parabolic-elliptic Keller-Segel type system, which is related to a simplified model of chemotaxis. Concerning the maximal range of existence of solutions, there are essentially two kinds of results: either global existence in time for general subcritical ($\|\rho_0\|_1<8\pi$) initial data, or blow--up in finite time for suitably chosen supercritical ($\|\rho_0\|_1>8\pi$) initial data with concentration around finitely many points. As a matter of fact there are no results claiming the existence of global solutions in the supercritical case. We solve this problem here and prove that, for a particular set of initial data which share large supercritical masses, the corresponding solution is global and uniformly bounded.
Apparent diffusion coefficient restriction in the white matter: going beyond acute brain territorial ischemia
Valentina Citton,Alberto Burlina,Claudio Baracchini,Massimo Gallucci,Alessia Catalucci,Sandro Dal Pos,Alessandro Burlina,Renzo Manara
Insights into Imaging , 2012, DOI: 10.1007/s13244-011-0114-3
Abstract: Neuroradiologists must be familiar with these features, thereby preventing misdiagnosis and inappropriate management.
Assessment of debris flow magnitude in small catchments of the lombardy alps: the val gola case study  [PDF]
Daniele de Wrachien, Stefano Mambretti
Agricultural Sciences (AS) , 2011, DOI: 10.4236/as.2011.21002
Abstract: Debris flows are among the most destructive of all water-related disasters. They mainly affect mountain areas in a wide range of morpho- climatic environments. Therefore, accurate pre-diction of their run out distances, magnitudes and velocities plays a role of paramount impor-tance, in order to plan and design appropriate structural and non-structural defence measures. In this context, a number of Authors have de-veloped methods feasible to evaluate the ten-dency of a catchment to generate debris flow, without giving an estimation of the magnitude. Other empirical procedures are based on the analysis of historical series of debris flow, oc-curred in similar environments, to assess the relationship between the catchment character-istics and the maximum movable debris vol-umes. In this paper, and with reference to Val Gola—a small catchment in the North-East Lom- bardy where debris flows frequently occur—a number of methods, belonging to each of the above mentioned categories, have been briefly reviewed and applied in order to evaluate their effectiveness and consistency.
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