Molecular dynamics studies on the NMR and X-ray structures of rabbit prion protein wild-type and mutants

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep, goats, mice, humans, chimpanzees, hamsters, cattle, elks, deer, minks, cats, chicken, pigs, turtles, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular protein into insoluble abnormally folded infectious prions and the conversion is believed to involve conformational change from a predominantly alpha-helical protein to one rich in beta-sheet structure. Such conformational changes may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show they have a low susceptibility to be infected, but in 2012 it was reported that rabbit prion can be generated (though not directly) and the rabbit prion is infectious and transmissible (Proceedings of the National Academy of Sciences USA 109(13): 5080-5). This paper studies the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants by MD techniques, in order to understand the specific mechanism of rabbit prion protein and rabbit prions.Comment: (The 2nd version of arXiv1304.7633

A Functional Misexpression Screen Uncovers a Role for Enabled in Progressive Neurodegeneration

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism

Efecto del captopril sobre la disfunción diastólica del venticulo izquierdo en el diabético joven insulinamente dependiente con microalbuminuria: una aproximación al tratamiento de la enfermedad del músculo cardíaco del diabético

Tesis doctoral inedita leida en la Universidad Autonoma de Madrid, Facultad de Medicina, Departamento de Medicina, 200

Extendiendo el modelo de programación de MPI

En el Modelo de programación definido por la librería MPI, una computación comprende uno o más procesos, los cuales se comunican a través de mensajes. Los procesos envían y reciben mensajes entre sí. En la mayoría de las implementaciones MPI, un número fijo de procesos es creado al inicio del programa. Cada proceso puede ejecutar distintos programas, de aquí que muchas veces se referencia al modelo de programación como MIMD (Múltiples Programas Múltiples Datos)Eje: Sistemas distribuidos y tiempo realRed de Universidades con Carreras en Informática (RedUNCI

Extendiendo el modelo de programación de MPI

En el Modelo de programación definido por la librería MPI, una computación comprende uno o más procesos, los cuales se comunican a través de mensajes. Los procesos envían y reciben mensajes entre sí. En la mayoría de las implementaciones MPI, un número fijo de procesos es creado al inicio del programa. Cada proceso puede ejecutar distintos programas, de aquí que muchas veces se referencia al modelo de programación como MIMD (Múltiples Programas Múltiples Datos)Eje: Sistemas distribuidos y tiempo realRed de Universidades con Carreras en Informática (RedUNCI

High pressure and temperatures during the early stages of tungsten deposition at Panasqueira revealed by fluid inclusions in topaz

International audienceThe Variscan vein-type Panasqueira W-Sn(Cu) deposit, one of the main tungsten deposits in Western Europe, has a long and complicated geological history. The first vein infillings, which consist of the quartz-wolframite association as well as the first generation of topaz, underwent significant deformation. As a consequence, most fluid inclusions of the earliest hydrothermal event are deformed and destroyed. Two preserved fluid inclusion assemblages are, however, found in the topaz overgrowth band and are dense aqueous-carbonic inclusions as well as dense CO2 dominated fluid inclusions. The P-T conditions of fluid trapping are constrained by using the intersection between isochores, as well as graphite-water equilibrium data and yield the following trapping conditions: 500 ± 20°C and 250 ± 20 MPa. These P-T conditions are incompatible with fluid unmixing. Fluid chemistry results from water-graphite equilibrium, probably in metapelites, at two distinct temperatures: around 450-500°C for the predominant aqueous-carbonic fluid, and higher temperatures of maximal 550°C for the CO2-rich fluid enriched in N2. These P-T estimates are consistent with deep crustal levels around 8-10 km depth and a high geothermal gradient around c. 60°C/km-1. The ascending non-magmatic fluids, enriched in volatiles, are essential in the ore genesis. The high thermal gradients may be related either to new magma pulse after the formation of the Panasqueira granite intrusion or to anomalous heat flux produced by the hot fluids ascending from migmatitic levels present at greater depth. This hypothesis necessitates to consider the role of a crustal weakness, which is attested both by the successive intrusions of several granitic magmas at the same place, and the presence of inherited quartz filled structures so-called Seixo-Bravo found only in the Panasqueira area