Identification of viral and host factors involved in the assembly, processing and nuclear export of influenza A viral mRNPs

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Revista española de orientación y psicopedagogía

Resumen basado en el de la publicaciónSe pretende comprender y explicar un proceso de intervención en orientación con el fin de establecer cuales deberían ser las condiciones y estrategias a seguir para que los agentes educativos se impliquen en un proceso de orientación. Se realiza una investigación evaluativa con carácter formativo, complementariedad metodológica y un proceso abierto de investigación. Para analizar la información se utiliza la triangulación entre métodos e intra métodos. Se recoge información de toda la población de profesorado, orientadores y servicio y una muestra de 953 alumnos. Se utiliza un diseño cuasiexperimental pretest-postest sin grupo control. Se explica cuál ha sido el proceso de formación y asesoramiento seguido y cómo se ha ido reconduciendo la intervención. Los resultados muestran que se ha logrado incluir la orientación en el aula, adquiriendo un carácter procesal, evolutivo y preventivo. Es necesario, por parte del profesorado, implicación y tiempo, cambios en el rol del orientador, un proceso de formación interno, temporizar actuaciones, trabajar en equipo y mantener la intervención por programas una vez finalizada la experiencia. El modelo de programas debe entenderse como un modelo organizativo de orientación que requiere explicar las funciones a realizar por los distintos agentes implicados.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 planta; 28014 Madrid; Tel. +34917748000; [email protected]

The Influenza A Virus NS1 Protein Interacts with the Nucleoprotein of Viral Ribonucleoprotein Complexes▿

The influenza A virus genome consists of eight RNA segments that associate with the viral polymerase proteins (PB1, PB2, and PA) and nucleoprotein (NP) to form ribonucleoprotein complexes (RNPs). The viral NS1 protein was previously shown to associate with these complexes, although it was not clear which RNP component mediated the interaction. Using individual TAP (tandem affinity purification)-tagged PB1, PB2, PA, and NP, we demonstrated that the NS1 protein interacts specifically with NP and not the polymerase subunits. The region of NS1 that binds NP was mapped to the RNA-binding domain

T Cell Energy Metabolism Is a Target of Glucocorticoids in Mice, Healthy Humans, and MS Patients

Glucocorticoids (GCs) are used to treat inflammatory disorders such as multiple sclerosis (MS) by exerting prominent activities in T cells including apoptosis induction and suppression of cytokine production. However, little is known about their impact on energy metabolism, although it is widely accepted that this process is a critical rheostat of T cell activity. We thus tested the hypothesis that GCs control genes and processes involved in nutrient transport and glycolysis. Our experiments revealed that escalating doses of dexamethasone (Dex) repressed energy metabolism in murine and human primary T cells. This effect was mediated by the GC receptor and unrelated to both apoptosis induction and Stat1 activity. In contrast, treatment of human T cells with rapamycin abolished the repression of metabolic gene expression by Dex, unveiling mTOR as a critical target of GC action. A similar phenomenon was observed in MS patients after intravenous methylprednisolon (IVMP) pulse therapy. The expression of metabolic genes was reduced in the peripheral blood T cells of most patients 24 h after GC treatment, an effect that correlated with disease activity. Collectively, our results establish the regulation of T cell energy metabolism by GCs as a new immunomodulatory principle

Properties of resonant activation phenomena

The phenomenon of resonant activation of a Brownian particle over a fluctuating barrier is revisited. We discuss the important distinctions between barriers that can fluctuate among up and down configurations, and barriers that are always up but that can fluctuate among different heights. A resonance as a function of the barrier fluctuation rate is found in both cases, but the nature and physical description of these resonances is quite distinct. The nature of the resonances, the physical basis for the resonant behavior, and the importance of boundary conditions are discussed in some detail. We obtain analytic expressions for the escape time over the barrier that explicitly capture the minima as a function of the barrier fluctuation rate, and show that our analytic results are in excellent agreement with numerical results

Spread of Infection and Lymphocyte Depletion in Mice Depends on Polymerase of Influenza Virus

SC35M is a mouse-adapted variant of the highly pathogenic avian influenza virus SC35. We have previously shown that interspecies adaptation is mediated by mutations in the viral polymerase and that it is paralleled by the acquisition of high pathogenicity for mice. In the present study, we have compared virus spread and organ tropism of SC35 and SC35M in mice. We show that SC35 virus causes mild bronchiolitis in these animals, whereas infection with the mouse-adapted SC35M virus leads to severe hemorrhagic pneumonia with dissemination to other organs, including the brain. In SC35M-infected animals, viral RNA and viral antigen were detected in monocytes and macrophages, and SC35M, unlike SC35, replicated in lymphocyte and macrophage cultures in vitro. SC35M did not induce an adequate cytokine response but, unlike SC35, caused severe lymphopenia in mice. These observations suggest that the high efficiency of the SC35M polymerase is responsible for infection and depletion of lymphocytes and other white blood cells, which results in immune suppression and systemic virus spread

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system