The Senegalese Sole Mx gene promoter contains a variable microsatellite region involved in the transcriptional

Interferons (IFNs) play a key role against viral infections by stimulating the expression of IFN stimulated genes, such as Mx. The transcriptional regulation of these genes in fish are poorly understood. The sequencing of the Senegalese sole (Solea senegalensis) Mx gene promoter revealed the presence of a guanosine-citosine rich region that contains a microsatellite, sited close to the translation start codon. The aim of the current study has been to determine the functional role of this region and to study its variability.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Senegalese sole (Solea senegalensis) ISG15: molecular characterization and in vivo interplay with viral infections

The interferon-stimulated gene 15 (Isg15) is strongly induced by type I interferon (IFN I), viral infection, and double-stranded RNA (poly I:C) in several fish species, suggesting that Isg15 protein could play a key role in fish innate immunity against viral diseases. Thus, the aim of the present study was to characterize the molecular structure and transcription pattern of the Senegalese sole (Solea senegalensis) Isg15 gene in response to viral infections. The molecular characterization shows that the Senegalese sole Isg15 gene codes for a typical Isg15 protein of 165 aa, containing two ubiquitin-like domains and one conserved LRLRGG conjugating motif at the C-terminal end. The untranslated 5´-end region exhibited the structure of an IFN-stimulated gene promoter, with two interferon stimulated response elements (ISRE). Pairwise alignments based on deduced amino acid sequences showed homologous relationships (72.5-74.2%) between the Isg15 of Senegalese sole and other pleuronectiforms. The Isg15 transcription has been studied in head kidneys of Senegalese sole inoculated with poly I:C and with different fish viruses: two Viral Haemorrhagic Septicaemia Virus (VHSV) isolates (highly pathogenic and non-pathogenic to sole), and one reassortant Viral Nervous Necrosis Virus (VNNV) isolate, composed of a RGNNV-type RNA1 and a SJNNV-type RNA2 (pathogenic to sole). These challenges showed that poly I:C induces Isg15 transcription from 3 to 72 h post-injection (p.i.), whereas the induction in response to viral infections started at 24-48 h p.i. The fast induction of Isg15 indicates the potential implication of this ISG in the antiviral state stablished by the IFN I system. On the other hand, the interaction between each virus and the IFN I system was evaluated in fish inoculated with poly I:C and subsequently (24 h later) challenged with the different viruses. This challenge showed a viral multiplication decrease in poly I:C treated animals compared with untreated fish. Besides, results showed that only both pathogenic isolates interfered negatively with the Isg15 stimulation triggered by poly I:C. These results suggest that the Isg15 might play an important role in host defense against RNA virus infection, and the pathogenic isolates used in this study may have mechanisms to evade or limit the Senegalese sole innate host defenses.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Estimulación del sistema mediado por interferón tipo I de lenguado senegalés (Solea senegalensis) en respuesta a infecciones por nodavirus

El lenguado senegalés es susceptible a la infección por el Virus de la Necrosis Nerviosa Viral (VNNV). Los betanodavirus se clasifican en cuatro genotipos, siendo los genotiposSJNNV, RGNNV y virus recombinantes RGNNV-SJNNV los que causan mortalidad en lenguado. En condiciones experimentales es el recombinante el que provoca mayor mortalidad. Las diferencias en la tasa de mortalidad pueden indicar variaciones en la interacción entre los distintos genotipos y el sistema inmune de lenguado. El sistema del interferón tipo I es un componente esencial de la respuesta inmune frente a infecciones virales, induciendo la expresión de genes que codifican proteínas antivíricas, tales como la Mx, la ISG15 y la PKR. El objetivo del presente trabajo ha sido cuantificar la transcripción de Mx, ISG15 y PKR en respuesta a infecciones por SJNNV, RGNNV y un recombinante RG-SJ.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Actividad antagonista de aislados del Virus de la Septicemia Hemorrágica Viral (VHSV) frente al sistema del interferón tipo I de lenguado senegalés

Senegalese sole (Solea senegalensis) is susceptible to marine Viral Haemorrhagic Septicaemia Virus (VHSV) isolates, but it is not affected by freshwater VHSV isolates. In addition, the sole type I interferon (IFN I) response is lower after infection with a marine VHSV isolate than in response to a freshwater isolate. In order to disclose the reasons of such differential response, in this study, the antagonistic activity of both kinds of VHSV isolates against IFN I system was characterised using an in vitro experimental system consisting of RTG-2 cells stably transfected with the luciferase gene under the control of the Senegalese sole mx promoter, which is one of the most induced interferon-stimulated genes. Our results showed that both isolates exert a dose-dependent negative effect on the response triggered by type I interferon, acting in the signal cascade pathway induced by IFN I, since the transcription of the gene coding for this cytokine is not affected. However, much higher levels of the non-pathogenic freshwater isolate were necessary to detect such antagonistic activity. Therefore, the inefficient antagonistic activity of the freshwater VHSV isolate might be involved in the lack of virulence of this isolate to Senegalese sole. Resumen El lenguado senegalés (Solea senegalensis) es susceptible a aislados marinos del Virus de la Septicemia Hemorrágica Viral (VHSV), pero no a aislados de agua dulce, frente a los cuales, además, hay una respuesta del sistema del interferón tipo I (IFN I) más intensa. Para averiguar las razones de esta respuesta diferencial, el objetivo que se plantea para el presente estudio es caracterizar y comparar la actividad antagonista de ambos aislados de VHSV frente al sistema del IFN I. Con este fin se utilizó un sistema experimental in vitro consistente en células RTG-2 transfectadas de forma estable con el gen de la luciferasa bajo el control del promotor del gen mx, que es uno de los genes inducidos por IFN I que más se estimulan en respuesta a infecciones víricas. Los resultados obtenidos muestran que ambos aislados de VHSV producen una interferencia negativa sobre la respuesta desencadenada por el IFN I. Dicha interferencia ocurre tras la síntesis de IFN I, y es dependiente de la dosis vírica. Sin embargo, para detectarla es necesario infectar las células con una dosis mucho más alta del aislado de agua dulce que del marino. Por lo tanto, la ineficiente actividad antagonista del aislado de agua dulce podría estar implicada en la no virulencia de este tipo de aislados en lenguado.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Estudio in vitro de la actividad antagonista de aislados del virus de la septicemia hemorrágica viral (VHSV) de distinto origen sobre el sistema del IFN tipo I

El lenguado senegalés (Solea senegalensis) es susceptible a aislados marinos del virus de la septicemia hemorrágica viral (VHSV); sin embargo, los VHSV patógenos para especies de agua dulce no son virulentos para especies marinas. Esta diferencia puede deberse al mecanismo antagonista que presenta cada tipo de aislado frente al sistema del interferón tipo I (IFN I). El objetivo de este estudio es caracterizar y comparar la actividad antagonista de dos aislados de VHSV de distinto origen. Para ello, se desarrolló un sistema experimental in vitro, consistente en células RTG-2 (trucha arcoíris), transfectadas con el gen de luciferasa bajo el control del promotor mx de lenguado, un efector antiviral estimulado por IFN I. Ambos aislados mostraron actividad antagonista dependiente de la multiplicidad de infección (MOI) y de la virulencia del virus en lenguado. Así, el aislado marino antagoniza a una MOI menor que el de agua dulce. Además, el antagonismo del marino ocurre exclusivamente a nivel del promotor mx de lenguado, no a nivel de transcripción de ifn I, ni de la cascada de activación de los genes estimulados por interferón. Por el contrario, el aislado de agua dulce también antagoniza la transcripción de genes mx endógenos (de trucha), pero no la transcripción de ifn I. El gen viral nv, implicado en la actividad antagonista, mostró un patrón de transcripción idéntico al del n (nucleoproteína) para el aislado de agua dulce, mientras que el nv marino inicia la transcripción más tarde que n. En cambio, en la línea celular de origen marino SAF-1, no se detecta este retraso en la transcripción de nv del aislado marino. El comportamiento diferencial de VHSV en función del origen del aislado y de la línea celular es un interesante aspecto a considerar en el estudio de la interacción VHSV-hospedador.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Strategy to improve comercial distribution in the ECOTUR travel agency

La pandemia de la COVID-19 ha obligado a replantearse las nuevas formas de gestión en todas las empresas en el sector turístico, entre ellas las agencias de viajes. Es por ello que la presente investigación está enfocada en desarrollar una estrategia para mejorar la distribución comercial en la agencia de viajes ECOTUR S.A, incluyendo objetivos y acciones que contribuyan a perfeccionar la gestión empresarial. La trayectoria metodológica permitió un diagnóstico de la situación que presenta la empresa respecto a la distribución comercial en el momento de accionar la misma en la etapa postpandemia. Para estos análisis se utilizaron varias herramientas como la Matriz DAFO; la Matriz de Evaluación de Factores Externos y la Matriz de Evaluación de Factores Internos. Asimismo, se identificaron los perfiles estratégicos del entorno y del proceso de distribución de la entidad. De igual forma, se aplicaron encuestas y entrevistas a especialistas de ECOTUR S.A, permitiendo trazar la estrategia con sus respectivos objetivos y planes de acciones.Today's tourism sector faces the most difficult scenario in recent times. The COVID-19 pandemic has forced a rethinking of new forms of management in all companies, including travel agencies. In order to redesign and adapt to the new normal, these entities need to seek strategies to improve internal processes, especially those associated with commercialization. That is why this research is focused on developing a strategy to improve commercial distribution in the travel agency ECOTUR S.A, including objectives and actions that contribute to improving business management. The methodological trajectory allowed a diagnosis of the current situation that the company presents with respect to commercial distribution, and the new actions in the post-pandemic stage. For these analyzes, several tools were used such as the SWOT Matrix; the External Factors Evaluation Matrix and the Internal Factors Evaluation Matrix. Likewise, the strategic profiles of the environment and the entity's distribution process were charted. Similarly, surveys and interviews with ECOTUR S.A specialists were applied, allowing the strategy to be drawn up with its respective objectives and action plans

El sistema del interferón tipo I protege a juveniles de lenguado senegalés (Solea senegalensis) frente a la infección por VHSV

El lenguado senegalés (Solea senegalensis) es susceptible a la infección por el Virus de la Septicemia Hemorrágica Viral (VHSV) bajo condiciones experimentales. El objetivo de este trabajo es determinar el papel del sistema del interferón tipo I de lenguado frente a las infecciones por VHSV. Para llevar a cabo este objetivo se realizó un ensayo en el que el sistema del IFN I de juveniles de lenguado se estimuló con poli I:C. Trascurridas 24 h estos mismos animales se inocularon con una dosis letal de un aislado de VHSV patógeno para lenguado. Los controles utilizados fueron: (I) animales inoculados con VHSV sin previa estimulación con poli I:C, (II) animales inoculados sólo con medio L15 y (III) animales inoculados únicamente con poli I:C.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The stimulation of the innate immune system by SJNNV protects juvenile european sea bass (Dicentrarchus labrax) against superinfection with RGNNV

In this study, viral replication and transcription of innate immunogenes have been determined by RT-real time-PCR (RT-qPCR) in the course of an experimental infection. Three different experimental conditions were considered: i) RGNNVinoculated animals; ii) SJNNV-inoculated animals and iii) animals inoculated with SJNNV and superinfected with RGNNV. Superinfection was performed 24 h after the SJNNV inoculation. Control animals were mocked-injected with L-15 medium. The RGNNV-infected group showed typical symptoms of the disease and displayed 76% cumulative mortality at the end of the experiment, whereas the mortality in the superinfected group was 4%, and no mortality was recorded in the SJNNV-inoculated group. The analysis of the Mx transcription by RT-qPCR showed a clearly differential induction of the sea bass innate immune system by RGNNV and SJNNV, since no transcription was recorded at any time tested (from 0 h to 48 h p.i.) after the RGNNV inoculation, whereas the injection of SJNNV resulted in an important increase of the Mx transcription from 24 h p.i. onwards. In the superinfected group the induction of the Mx gene transcription follows the same patterns that the ones described for the groups inoculated with SJNNV and RGNNV separately. These results suggest that the induction of the IFN mediated system by the previous infection with SJNNV could be responsible for the decrease in the mortality recorded in the superinfected group, protecting sea bass of the posterior infection with RGNNV.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Enfrentando los riesgos socionaturales

El objetivo del libro es comprender la magnitud de los Riesgos Socionaturales en México y Latinoamérica, para comprender el peligro que existe por algún tipo de desastre, ya sea inundaciones, sismos, remoción en masa, entre otros, además conocer qué medidas preventivas, correctivas y de contingencias existen para estar atentos ante alguna señal que la naturaleza esté enviando y así evitar alguna catástrofe. El libro se enfoca en los aspectos básicos de análisis de los peligros, escenarios de riesgo, vulnerabilidad y resiliencia, importantes para la gestión prospectiva o preventiva