MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells

A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protei

Theoretical and numerical studies of wave-packet propagation in tokamak plasmas

Theoretical and numerical studies of wave-packet propagation are presented to analyze the time varying 2D mode structures of electrostatic fluctuations in tokamak plasmas, using general flux coordinates. Instead of solving the 2D wave equations directly, the solution of the initial value problem is used to obtain the 2D mode structure, following the propagation of wave-packets generated by a source and reconstructing the time varying field. As application, the 2D WKB method is applied to investigate the shaping effects (elongation and triangularity) of tokamak geometry on the lower hybrid wave propagation and absorbtion. Meanwhile, the Mode Structure Decomposition (MSD) method is used to handle the boundary conditions and simplify the 2D problem to two nested 1D problems. The MSD method is related to that discussed earlier by Zonca and Chen [Phys. Fluids B 5, 3668 (1993)], and reduces to the well-known "ballooning formalism" [J. W. Connor, R. J. Hastie, and J. B. Taylor, Phys. Rev. Lett. 40, 396 (1978)], when spatial scale separation applies. This method is used to investigate the time varying 2D electrostatic ITG mode structure with a mixed WKB-full-wave technique. The time varying field pattern is reconstructed and the time asymptotic structure of the wave-packet propagation gives the 2D eigenmode and the corresponding eigenvalue. As a general approach to investigate 2D mode structures in tokamak plasmas, our method also applies for electromagnetic waves with general source/sink terms, either by an internal/external antenna or nonlinear wave interaction with zonal structures.Comment: 24 pages, 14 figure

An outline of polar spaces: basics and advances

This paper is an extended version of a series of lectures on polar spaces given during the workshop and conference 'Groups and Geometries', held at the Indian Statistical Institute in Bangalore in December 2012. The aim of this paper is to give an overview of the theory of polar spaces focusing on some research topics related to polar spaces. We survey the fundamental results about polar spaces starting from classical polar spaces. Then we introduce and report on the state of the art on the following research topics: polar spaces of infinite rank, embedding polar spaces in groups and projective embeddings of dual polar spaces

Melatonin in Alzheimer's disease and other neurodegenerative disorders

Increased oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological phenomena associated with neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the age-related decline in the production of melatonin may contribute to increased levels of oxidative stress in the elderly, the role of this neuroprotective agent is attracting increasing attention. Melatonin has multiple actions as a regulator of antioxidant and prooxidant enzymes, radical scavenger and antagonist of mitochondrial radical formation. The ability of melatonin and its kynuramine metabolites to interact directly with the electron transport chain by increasing the electron flow and reducing electron leakage are unique features by which melatonin is able to increase the survival of neurons under enhanced oxidative stress. Moreover, antifibrillogenic actions have been demonstrated in vitro, also in the presence of profibrillogenic apoE4 or apoE3, and in vivo, in a transgenic mouse model. Amyloid-β toxicity is antagonized by melatonin and one of its kynuramine metabolites. Cytoskeletal disorganization and protein hyperphosphorylation, as induced in several cell-line models, have been attenuated by melatonin, effects comprising stress kinase downregulation and extending to neurotrophin expression. Various experimental models of AD, PD and HD indicate the usefulness of melatonin in antagonizing disease progression and/or mitigating some of the symptoms. Melatonin secretion has been found to be altered in AD and PD. Attempts to compensate for age- and disease-dependent melatonin deficiency have shown that administration of this compound can improve sleep efficiency in AD and PD and, to some extent, cognitive function in AD patients. Exogenous melatonin has also been reported to alleviate behavioral symptoms such as sundowning. Taken together, these findings suggest that melatonin, its analogues and kynuric metabolites may have potential value in prevention and treatment of AD and other neurodegenerative disorders

AN INTERDISCIPLINARY APPROACH FOR THE SEISMIC VULNERABILITY ASSESSMENT OF HISTORICAL CENTRES IN MASONRY BUILDING AGGREGATES: APPLICATION TO THE CITY OF SCARPERIA, ITALY

Abstract. The seismic vulnerability of masonry building aggregates is very difficult to determine, since it is affected by many uncertainties. The most uncertain quantities concern the historical periodization of structural aggregates. Moreover, the studies made at the urban scale can hardly be thorough, and usually the knowledge achieved on the single units is not fully satisfactory, so that the structural designer has to deal with uncompleted architectonical surveys and partial data; one of the most important problems concerns the lack of knowledge about the boundary conditions between adjacent structures. In order to perform mechanical analyses, an extensive knowledge of materials and techniques adopted is required. In this paper, an integrated methodology for the seismic assessment of building aggregate is presented. It concerns a multidisciplinary knowledge-based approach calibrated over the historical centres and the urban aggregates; the procedure joins different aspects, such as the use of modern technologies for an integrated knowledge, plans reconstructions through archival documents, laser scanner digital survey of urban fronts, non-destructive investigations of the materials. GIS and BIM platforms have been used to implement and collect data in order to perform detailed analyses. The information allowed to assess the seismic vulnerability of the building aggregates and the expected damage scenarios through empirical methodologies. The city of Scarperia, founded a few kilometres from Florence during the Medieval Age and characterized by a medium seismicity, has been chosen as a case study for the presented procedure

La melatonina en la enfermedad de Chagas: Su posible valor terapéutico

La enfermedad de Chagas es un problema grave de salud en América Latina, causando cerca de 50 000 muertes al año y unos 18 millones de infectados. Alrededor del 25-30% de los pacientes infectados con Trypanosoma cruzi desarrollan la forma crónica de la enfermedad. La respuesta de defensa ante el T. cruzi depende de la inmunidad innata y adquirida con la participación de macrófagos, células “natural killer”, linfocitos T y B, y la producción de citoquinas proinflamatorias de tipo Th-1. Además, el aumento en la producción de óxido nítrico (NO) en los macrófagos lleva a una acción microbicida eficaz necesaria para controlar la parasitemia. La melatonina es detectable en T. cruzi y podría desempeñar un papel en la promoción de la infección como lo hace en el paludismo, mientras que, cuando se administra en dosis farmacológicas altas durante la fase aguda de la infección por T. cruzi, disminuye la parasitemia, aun en presencia de una reducción de la producción de NO. Durante la progresión de la enfermedad de Chagas a la cronicidad, el estrés oxidativo aumentado con el concomitante daño miocárdico podría reducirse por la administración de melatonina, de reconocida acción antioxidante. Se propone como un nuevo enfoque complementario en el tratamiento de la enfermedad de Chagas la administración durante la fase aguda de un agonista MT1/MT2 de la melatonina como el ramelteon, que carece de actividad antioxidante y podría no afectar a la producción de NO, y de melatonina durante la fase crónica de en dosis suficientemente altas como para disminuir el daño oxidativo y prevenir la miocardiopatía.Chagas’ disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO) production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1/MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas´ diseaseFil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Álvarez, Carlos B.. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentin