1,365 research outputs found

    Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics.

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    The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics

    Direct Cell-to-Cell Transmission of Respiratory Viruses: The Fast Lanes

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    Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2]. Direct cell-to-cell spread of infections has several advantages. The first is efficiency: genomic cargo is delivered directly to cells rather than being randomly released into the environment. The second is speed: appropriation of cellular protein trafficking infrastructure allows faster spread within tissues. The third is barrier avoidance: intrinsic immunity and other barriers interfering with entry or post-entry steps in target cells can be bypassed. The fourth is humoral immunity evasion: limited exposure time to the extracellular space allows evasion of neutralizing antibodies

    Migración de registros bibliográficos a Marc21 : problemáticas, técnicas y experiencias en torno a la implementación del sistema Digibepe (Koha) de Conabip

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    A partir de la experiencia de la Red Puntobiblio en la construcción de un catálogo colectivo de bibliotecas de diferentes tipologías: populares, escolares, especializadas, etc. la Comisión Nacional Protectora de Bibliotecas Populares solicitó a la responsable técnica del proyecto Puntobiblio, Verónica Lencinas, y a un informático especializado, Pablo Bianchi, la presentación de un proyecto que permitiera implementar un sistema de gestión bibliotecario actualizado en las bibliotecas populares argentinas con el objeto de reemplazar el sistema Sigebi que había quedado obsoleto. Una vez aprobado el proyecto que e iniciado la implementación del sistema Digibepé (Koha), fue necesario migrar los datos, sobre todo los datos de catálogos de bibliotecas al formato Marc21. Se migraron no solamente catálogos en Sigebi sino también aquellos provenientes de Aguapey, Winisis, Troya, Pérgamo, Catalis, OpenMarcoPolo y sistemas propios realizados mayoritariamente en MS Excell, Clipper, FoxPro y MS Access. En el presente aporte se describen estrategias y técnicas utilizadas en la migración de datos diversos al formato Marc21 tal como lo implementa el sistema Digibepé (Koha) y la capacitación realizada a los nodos regionales de asistencia técnica, "Nodos Digibepés", a fin de capacitar a bibliotecarios en la migraciones de datos.http://eprints.rclis.org/19908/Fil: Lencinas, Verónica. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Bibliotecología; Argentina.Fil: Lencinas, Verónica. Universidad Nacional de Córdoba. Biblioteca Observatorio Astronómico de Córdoba; Argentina.Fil: Cattaneo, Roberto. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Bibliotecología; Argentina.Fil: Cattaneo, Roberto. Universidad Nacional de Córdoba. Biblioteca Observatorio Astronómico de Córdoba; Argentina.Otras Ciencias de la Computación e Informació

    Tyrosine 110 in the measles virus phosphoprotein is required to block STAT1 phosphorylation

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    AbstractThe measles virus (MV) P gene encodes three proteins: P, an essential polymerase cofactor, and C and V, which have multiple functions including immune evasion. We show here that the MV P protein also contributes to immune evasion, and that tyrosine 110 is required to block nuclear translocation of the signal transducer and activator of transcription factors (STAT) after interferon type I treatment. In particular, MV P inhibits STAT1 phosphorylation. This is shown not only by transient expression but also by reverse genetic analyses based on a new functional infectious cDNA derived from a MV vaccine vial (Moraten strain). Our study also identifies a conserved sequence around P protein tyrosine 110 as a candidate interaction site with a cellular protein

    Soothing and anti-itch effect of quercetin phytosome in human subjects: A single-blind study

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    Background: We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita\uc2\uae, 1% cream for external use, a formulation characterized by a phospholipids-based delivery system. Patients and methods: The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita\uc2\uae 1% cream, 2 mg/cm2; placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine). Results: Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (\ue2\u80\u9310.05% [P=0.00329] for quercetin phospholipids 1% vs \ue2\u80\u9314.05% [P=0.00046] for the positive control). Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (\ue2\u80\u9313.25% and \ue2\u80\u9312.23% for dexchlorpheniramine 1%, respectively). Similar findings were reported for the other tested parameters. Conclusion: Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able to reduce redness, itching, and inflammation of damaged skin; it may also help restore skin barrier function, increasing hydration, and reducing water loss

    Chemosensory Receptors in the Larval Maxilla of Papilio hospiton

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    Among the butterflies of the genus Papilio (Lepidoptera: Papilionidae), Papilio hospiton (Géné) has a geographical distribution limited to the Mediterranean islands of Sardinia (Italy) and Corsica (France). This is mainly due to the host range that includes only a few plant species of Apiaceae and Rutaceae growing on these islands. In a previous electrophysiological investigation conducted on the maxillary gustatory system of larvae of P. hospiton and its closely phylogenetically related species Papilio machaon, a significantly higher spike activity was shown for the gustatory neurons of lateral and medial styloconic sensilla in P. hospiton when bitter compounds were tested. This effect was possibly correlated to the limited host choice range for P. hospiton. To shed light on the molecular aspects of this phenomenon, we investigated the expression pattern of sensory-related sequences by conducting a transcriptomic analysis from total RNA isolates of P. hospiton larval maxillae. We identified several transcripts that may be involved in taste (one gustatory receptor, one divergent ionotropic receptor, and several transient receptor potential channels, TRPs) as well as transcripts supporting an olfactory function for this appendage, including odorant receptors (ORs), antennal ionotropic receptors (A-IRs), sensory neuron membrane proteins (SNMPs), and odorant-binding proteins (OBPs). We used Human Embryonic Kidney (HEK293A) cells to heterologously express two of the identified receptors, PhospOR1 and PhospPain, together with their orthologs from P. machaon, for functional characterization. While our data suggest no activation of these two receptors by the ligands known so far to activate the electrophysiological response in larval maxillary neurons of Papilio species, nor temperature activation of both Papilio TRPA-channel Painless, they represent the first attempt in connecting neuronal activity with their molecular bases to unravel diet specialization between closely related Papilio species
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