Mutagenesis-Mediated Decrease of Pathogenicity as a Feature of the Mutant Spectrum of a Viral Population

Background: RNA virus populations are heterogeneous ensembles of closely related genomes termed quasispecies. This highly complex distribution of variants confers important properties to RNA viruses and influences their pathogenic behavior. It has been hypothesized that increased mutagenesis of viral populations, by treatment with mutagenic agents, can induce alterations in the pathogenic potential of a virus population. In this work we investigate whether mutagenized foot-and-mouth disease virus (FMDV) populations display changes in their virulence in mice. Methodology and Principal Findings: FMDV C-S8c1 was passaged in BHK cells in the presence of the mutagenic agent ribavirin. Decline in viral titer and viral RNA progeny was observed in the first passage, fluctuating around a constant value thereafter. Hence, the specific infectivity remained stable during the passages. The viral population harvested from passage 9 (P9 R) showed decreased virulence in mice, with a lethal dose 50 (LD 50) >10 4 PFU, as compared with LD 50 of 50 PFU of the parental population FMDV C-S8c1. This decrease in virulence was associated to a 20-fold increase in the mutation frequency of the P9 R population with respect to C-S8c1. Interestingly, individual biological clones isolated from the attenuated population P9 R were as virulent as the parental virus C-S8c1. Furthermore, a mixed population of C-S8c1 and P9 R was inoculated into mice and showed decreased virulence as compared to C-S8c1, suggesting that population P9 R is able to suppress the virulent phenotype of C-S8c1. Conclusion: Ribavirin-mediated mutagenesis of an FMDV population resulted in attenuation in vivo, albeit a large proportion of its biological clones displayed a highly virulent phenotype. These results, together with the suppression of C-S8c1 by mutagenized P9 R population, document a suppressive effect of mutagenized viral quasispecies in vivo, and suggest novel approaches to the treatment and prevention of viral diseases. © 2012 Sanz-Ramos et al.CISA-INIA Centro de Investigación en Sanidad Animal; Ministerio de Ciencia e Innovación (MCINN); 228394-NADIR-Integrating Activities 7th EU; Fundación Ramón ArecesPeer Reviewe

A replication analysis of foot-and-mouth disease virus in swine lymphoid tissue might indicate a putative carrier stage in pigs

Foot-and-mouth disease virus (FMVD), one of the most contagious viruses of cloven-hoofed animals, may cause a prolonged, asymptomatic but persistent infection in ruminants, named the "carrier state". However, it remains an open question whether this carrier state occurs in pigs. Here we present quantitative analyses of the duration of FMDV RNA and infectivity in lymphoid and epithelial tissues in experimentally infected pigs with FMDV C-S8c1. The data indicated that although FMDV RNA remained in blood until day 14 post-infection (pi), viremia was cleared by day 7 pi. However, all tissues tested were positive for FMDV until day 14-17 pi. Interestingly, the specific infectivity of FMDV in these tissues was in some cases even higher than the FMDV C-S8c1. We therefore propose that a "pseudopersistent state" may occur in pigs in which virus replicates in lymphoid tissues for a prolonged period of time, thereby representing a potential source of virus

TIC para la inclusión. Proyecto investigativo sobre la voz del estudiante en España

ABSTRACT: This article is the result of a research project developed over 4 years (2011-15) in 13 schools in the region of Cantabria (Spain). In this research, students from different levels of education designed and implemented school improvement processes within a model of the student voice (SV) inspired by the pedagogy of participation and inclusion. This paper describes some of these experiences mediated by technology (photographs, 2.0 devices and video) in order to analyse what opportunities these devices offer as a means for contributing to a more participative and democratic school, where the stu¬dent voice is a tool for change.RESUMEN: Este artículo es el resultado de un proyecto investigativo de¬sarrollado durante 4 años (2011-15) en 13 escuelas de la re¬gión de Cantabria (España). En esta investigación, estudiantes de diferentes niveles de educación diseñaron e implementa¬ron procesos de mejoramiento escolar dentro de un modelo de Voz del Estudiante (VdE) inspirado en la pedagogía de la participación y la inclusión. Este artículo describe algunas de esas experiencias mediadas por la tecnología (fotografías, dis¬positivos 2.0 y vídeo) con el fin de analizar qué oportunidades ofrecen estos dispositivos como medio para contribuir a una escuela más democrática y participativa, donde la voz de los estudiantes es una herramienta para el cambio

Formulación de un concentrado de ácidos grasos poliinsaturados omega-3 con lecitina de soja mediante emulsificación por ultrasonidos

Póster presentado en: I Congreso CyTA Junior: 19 de mayo de 2017. IX Congreso CyTA-CESIA, Ayer, hoy y mañana de la Ciencia y Tecnología de los Alimentos, 16-19 de mayo de 2017, MadridJCyL y FEDER por la financiación del proyecto BU055U1

Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior

Introduction: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. Case Report: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandi - bulectomy with an alveolar inferior nerve lateralization was performed. Conclusions: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed

Supercritical carbon dioxide extraction of quinoa oil: Study of the influence of process parameters on the extraction yield and oil quality

The supercritical CO2 extraction of oil from four different quinoa varieties has been studied in this work. For this purpose, the influence of extraction temperature (40–60 °C), pressure (20–40 MPa) and raw material size (250–1000 μm) on the extraction rate has been considered. The extraction rate resulted to be faster the higher the pressure whereas the temperature had less influence on the extraction kinetics. The experimental data were modelled using the Sovova’s kinetic model. The quality of the oil extracted has been evaluated in terms of antioxidant activity (AA), fatty acid profile and tocopherol content. The highest AA was obtained for quinoa oil extracted at 40 MPa and 40 °C; this oil presented high content of polyunsaturated fatty acids (63% of the total) and significant amount of tocopherols (2.5 mg/g oil). Quinoa oil extracted using CO2 presented higher antioxidant capacity and tocopherol content than quinoa oil extracted with hexane, regardless the quinoa variety used.Junta de Castilla y León and the European Regional Development Fund (ERDF - FEDER) for the financial support of project BU055U1

Identification of targets for prevention of peritoneal catheter tunnel and exit-site infections in low incidence settings

[Abstract] ♦ Background: Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections. ♦ Objective: To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections. ♦ Method: Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis. ♦ Main results: The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p = 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p = 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ≥ 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients. ♦ Conclusions: Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI

Kinetic study of the semi-continuous extraction/hydrolysis of the protein and polysaccharide fraction of the industrial solid residue from red macroalgae by subcritical water

The valorization of the underexploited solid residue after agar extraction from red marine algae was studied by subcritical water treatment. Experiments were carried out in two different semi-continuous fix-bed reactor configurations at 185 ºC at different subcritical water residence times. The use of a by-pass section allowed to heat the water previous contact to the biomass, avoiding the exposure of the sample to high temperatures during the heating procedure and reducing the formation of degradation products. Higher hydrolysis yields were obtained for the protein fraction (reaching 96.1%) than for the carbohydrate fraction (reaching 45.7%, 11.3%, 27.5% and 57.6% for galactans, glucans, arabinans and uronic acids, respectively). With the decrease of the residence time, by increasing the flow rate, higher initial hydrolysis rates were obtained due to enhancing diffusion of the hydrolysis products into the bulk solution. It was determined a similar dependence of the initial hydrolysis rates on the residence time for the carbohydrate oligomers and total protein fraction, but the release of free amino acids was less dependent on increasing flow rate due to higher diffusion coefficients for small molecules.Agencia Estatal de Investigación (Spain) [grant number PID2019–104950RB-I00 / AEI / 10.13039/501100011033], the Junta de Castilla y León (JCyL) and the European Regional Development Fund (ERDF) [grant numbers BU301P18 and BU050P20] E. Trigueros and P. Alonso-Riaño predoctoral contracts were funded by the JCyL and the European Social Fund (ESF) by ORDEN EDU/574/2018, de 28 de mayo and ORDEN EDU/556/2019, de 5 de junio, respectively. The C. I. K. Diop contract was funded by the European Commission, Horizon 2020 program through the Marie-Curie Individual Fellowship (H2020-MSCA-IF-2019), with regards to the ALGWAS-BIOR project (Grant agreement number 898804)

La exención fiscal a la Iglesia católica por el ejercicio de actividades sin una finalidad estrictamente religiosa puede constituir ayudas de estado prohibidas por el Derecho Comunitario: Análisis de la STJUE de 27 de junio de 2017, asunto C-74/16

El presente comentario tiene por objeto el análisis e implicaciones de la Sentencia dictada el 27 de junio de 2017 por el Tribunal de Justicia de la Unión Europea a la cuestión prejudicial planteada por el juez nacional sobre la posible incompatibilidad con el Derecho Comunitario de la exención que se ha venido concediendo a la Iglesia católica con base en el Acuerdo Económico con la Santa Sede de 1979. Esta sentencia viene a constituir un punto de inflexión pues declara contrarias al Tratado de Funcionamiento de la Unión Europea las ayudas públicas que reciben entidades dependientes de la Iglesia católica en forma de beneficios fiscales, cuando se ejercen actividades que no sean estrictamente religiosas. Doctrina que es aplicable al resto de confesiones religiosas, en su caso, así como a otras entidades y beneficios fiscales contemplados en nuestras normas tributarias, v. gr. Ley 49/2002, de 23 de diciembre, de régimen fiscal de las entidades sin fines lucrativos y de los incentivos fiscales al mecenazgo o la Ley 50/2002, de 26 de diciembre, de Fundaciones

New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines

Background: New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260). Principal Finding: Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV. Conclusions: The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms. © 2010 Rodríguez-Calvo et al.Ministerio de Ciencia e Innovación, Spain, and European Union, Network of Excellence, EPIZONE (Contract # FOOD-CT-2006-016236). CIBERehd (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Work at Centro de Biología Molecular ‘‘Severo Ochoa’’ (CISC-UAM) was supported by an institutional grant from Fundación Ramón Arece