Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

11 p.

Los determinantes de la rentabilidad primaria de los bonos de titulización hipotecaria: la influencia de las estructuras multitramo

[ES] Este artículo analiza los determinantes de la rentabilidad primaria de los bonos de titulización hipotecaria (conocidos en la literatura como mortgage backed securities, o MBS) emitidos en España durante el periodo 1993-2011, periodo en el que el mercado español llegó a convertirse en el más importante de Europa continental. Los resultados obtenidos sobre el análisis de la población completa de MBS emitidos (262 tramos configurados sobre 94 fondos de titulización) indican que la estructuración multitramo de los MBS ha ayudado a reducir el riesgo percibido global de las emisiones de MBS, mediante la generación de mercados más completos y la reducción de los problemas derivados de la existencia de asimetrías informativas implícitas en el proceso de selección de los activos transmitidos por parte de la entidad cedente. Esta reducción del riesgo percibido ha tenido un efecto directo sobre la rentabilidad ofrecida por los bonos de titulización emitidos. Además, no se encuentran evidencias de que la emisión de MBS persiga la transmisión efectiva de riesgos, más bien al contrario. Las Entidades de crédito, por lo general, han retenido los tramos de primeras pérdidas, lo que ha contribuido a mantener en niveles muy bajos (por debajo de la rentabilidad de la deuda soberana) la rentabilidad ofrecida por los MBS. Precisamente, el escaso diferencial ofrecido por los bonos de titulización se debe a que los tramos retenidos no han ofrecido primas de rentabilidad ajustadas al riesgo inherente.

Muscle wasting in myotonic dystrophies: a model of premature aging

Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia ll/Iyotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

Proteomic Analysis of the Ubiquitin Landscape in the Drosophila Embryonic Nervous System and the Adult Photoreceptor Cells

Background Ubiquitination is known to regulate physiological neuronal functions as well as to be involved in a number of neuronal diseases. Several ubiquitin proteomic approaches have been developed during the last decade but, as they have been mostly applied to non-neuronal cell culture, very little is yet known about neuronal ubiquitination pathways in vivo. Methodology/Principal Findings Using an in vivo biotinylation strategy we have isolated and identified the ubiquitinated proteome in neurons both for the developing embryonic brain and for the adult eye of Drosophila melanogaster. Bioinformatic comparison of both datasets indicates a significant difference on the ubiquitin substrates, which logically correlates with the processes that are most active at each of the developmental stages. Detection within the isolated material of two ubiquitin E3 ligases, Parkin and Ube3a, indicates their ubiquitinating activity on the studied tissues. Further identification of the proteins that do accumulate upon interference with the proteasomal degradative pathway provides an indication of the proteins that are targeted for clearance in neurons. Last, we report the proof-of-principle validation of two lysine residues required for nSyb ubiquitination. Conclusions/Significance These data cast light on the differential and common ubiquitination pathways between the embryonic and adult neurons, and hence will contribute to the understanding of the mechanisms by which neuronal function is regulated. The in vivo biotinylation methodology described here complements other approaches for ubiquitome study and offers unique advantages, and is poised to provide further insight into disease mechanisms related to the ubiquitin proteasome system.