Cytoplasmic CUG RNA Foci Are Insufficient to Elicit Key DM1 Features

The genetic basis of myotonic dystrophy type I (DM1) is the expansion of a CTG tract located in the 3′ untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG)400 repeat tract was positioned 3′ of the termination codon and 5′ of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA aggregates is an important variable that influences toxicity and support the hypothesis that small molecules that increase the rate of transport of the mutant DMPK RNA from the nucleus into the cytoplasm may significantly improve DM1 pathology

The problem of ventricular tachycardia with torsade de pointes and of its rational treatment

[No abstract available

DIETOTERAPIA EN POSTCOLECISTECTOMÍA DE PACIENTES INGRESADOS EN EL HOSPITAL NAPOLEÓN DÁVILA CÓRDOVA.

LA DIETOTERAPIA HA DADO PASOS IMPORTANTES Y CADA VEZ SON MÁS LOS PROFESIONALES DE LA MEDICINA QUE CONSIDERAN IMPORTANTE ESTIMULAR A SUS PACIENTES PARA QUE RECIBAN UNA ADECUADA NUTRICIÓN. ESTE PLANTEAMIENTO TOMA COMO REFERENCIA LA INCIDENCIA QUE TIENE LA DIETOTERAPIA EN LA POSTCOLECISTECTOMÍA DE PACIENTES INGRESADOS EN EL HOSPITAL DEBIDO AL DESCONTROL ALIMENTICIO Y UN DESBALANCE NUTRICIONAL...EL PRESENTE TRABAJO DE INVESTIGACIÓN TIENE COMO OBJETIVO: DETERMINAR LA INCIDENCIA DE LA DIETOTERAPIA EN POSTCOLECISTECTOMÍA DE PACIENTES INGRESADOS EN EL HOSPITAL NAPOLEÓN DÁVILA CÓRDOVA DE CHONE DURANTE EL SEGUNDO SEMESTRE DEL 2014. EN LO ESPECÍFICO: DEFINIR LA FUNDAMENTACIÓN TEÓRICA DE LA DIETOTERAPIA; EXPLICAR LA DIETOTERAPIA ADMINISTRADA A PACIENTES EN POSTCOLECISTECTOMÍA..

La defensa del Jurel en la OROP del Pacífico Sur

El aprovechamiento del recurso pesquero depende de la propia naturaleza de los mares y las características migratorias de los peces. Así las cosas, la división de intereses entre Estados costeros y ribereños con Estados que pescan a distancia, ha marcado la pauta de la regulación internacional en relación con el aprovechamiento de este recurso natural. En este contexto, el presente artículo trata de explicar brevemente el contexto de regulación internacional relacionado con la pesca en altamar. Ello con la finalidad de contextualizar la defensa exitosa del Perú por mantener la soberanía en sus aguas jurisdiccionales, en el marco de los acuerdos que dieron origen a la Organización Regional de Ordenamiento Pesquero del Pacífio Sur.The exploitation of the shing resource depends on the nature of the seas and the migratory characteristics of shes. Thus, the division of interests between coastal States and coastal States with States that sh at a distance, has set the pattern of international regulation in relation to the use of this natural resource. In this context, this article tries to briefly explain the context of international regulation related to the shing industry on the high seas. This in order to contextualize the successful defense of Peru to maintain sovereignty in its jurisdictional waters, within the framework of the agreements that gave rise to the South Pacific Regional Fisheries Management Organization

The problem of ventricular tachycardia with torsade de pointes and of its rational treatment

[No abstract available