Editorial: Emerging Mechanisms in Neuronal Signaling: From Cell Biology to Pathogenesis

Unraveling the molecular processes involved in the genesis, differentiation, and cell death of the nervous system is an intense and continual interest of the neuroscience community. In recent years, the preponderance of research focused upon signal transduction mechanisms relying on protein cascades, but more information is needed on the role and function of other molecular mechanisms. These molecular mechanisms include but not limited to: lipid mediators (sphingolipids, fatty acids, glycerophospholipids, etc.), lipid-binding proteins (ApoD, PPAR, etc.), protein-lipid interactions (c-Fos-lipid synthesizing enzymes), protein misfolding and not fully characterized membrane-protein receptors.Fil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Alonso, Alejandra del Carmen. College of Staten Island; Estados Unidos. City University of New York; Estados Unido

Development of in vitro systems to study IFN signalling in gilthead seabream (Sparus aurata)

Type I interferon (IFN I) triggers specific signalling pathways leading to the activation of the innate immune defence of vertebrates against viral infections. In contrats, type II IFN (IFN II) is generally accepted to be part of the adaptive response. Among IFN I-stimulated genes, those coding the Mx proteins play a main role due to the direct antiviral activity of these proteins. The study of Mx genes in gilthead seabream, one of the most important species in the Mediterranean aquaculture, is especially interesting, as this species displays a high natural resistance to viral diseases, and behaves as asymptomatic carrier and/or reservoir of several viruses, such as viral nervous necrosis virus (VNNV), infectious pancreatic necrosis virus (IPNV), and viral haemorrhagic septicaemia virus (VHSV), which are pathogenic to other fish species. Three Mx genes (Mx1, Mx2, and Mx3) have been identified in S. aurata, showing the three proteins a wide spectrum of antiviral activity. The structure of the three promoters (pMx1, pMx2 and pMx3) has been disclosed, and their response to IFN I, IPNV and VHSV indicated a clear induction of the three promoters, with some differences in the kinetics and magnitude of the response. Several studies evidenced the important role of Mx transcription regulation on virus-host interaction: i) Mx promoters can respond to both IFN I and IFN II, thus Mx might be the link between innate and adaptive immunity; ii) Mx activation is blocked by several viruses, thus Mx transcription is the target of their IFN I antagonistic activity; and iii) A fish cell line modified with the promoter of a fish Mx gene was used to measure viraemia in serum with high sensitivity. Therefore, assessing the regulatory mechanisms controlling the transcription of fish Mx genes could significantly contribute to both, understanding virus-host interactions, and designing strategies to control viral infections. In our case, this approach can also give light to understand the successful antiviral strategies developed by gilthead seabream in nature. Thus, the purpose of the present work was to develop three stable transgenic cell lines expressing the firefly luciferase gene under the control of the gilthead seabream Mx promoters. These in vitro systems were established and their response to poly I:C, and to two viral infections was characterized. In the case of IPNV, a clear antagonistic activity was observed for pMx2, as the activity of the promoter was 78.53% lower, however, this effect was not observed for pMx1 and pMx3. When cells were infected with VHSV, no changes in the promoters’ activity were detected, thus indicating that seabream Mx promoters are not targeted by VHSV antagonistic activity. These results confirm the specificity of the interactions between each virus/promoter combination, and support the use of the three cell lines developed as useful tools to characterize virus-host interactions in this species. Further studies aimed at the identification of the molecular mechanisms behind our observations will allow us to get more insight into this complex system.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Gilthead seabream (Sparus aurata) Mx proteins show positive and negative synergy in their antiviral activity

Due to their direct antiviral activity, Mx proteins play a main role in the response mediated by the type I interferon against viral infections. The study of the farmed fish gilthead seabream Mx genes is specially interesting, since this species displays an unusually high natural resistance to viral diseases, becoming a potential asymptomatic carrier and/or reservoir for several viruses pathogenic to other fish species. Gilthead seabream has three Mx proteins (Mx1, Mx2 and Mx3) that, separately, display antiviral activity against a wide range of viruses, showing interesting differences in their antiviral specificities. In this work, the possible synergy between the three Mx isoforms has been studied using in vitro systems, consisting of permanently transfected CHSE-214 cells expressing two or the three gilthead seabream Mx proteins. The antiviral activity of these Mx combinations has been tested against the infection by the Infectious Pancreatic Necrosis Virus (IPNV), the Viral Haemorrhagic Septicaemia Virus (VHSV) and the European Sheatfish Virus (ESV) in cells inoculated at 0.1 and 0.01 multiplicity of infection (MOI). The antiviral effect was evaluated by viral titration (TCID50 method). Interestingly, a positive synergistic effect in the antiviral activity against ESV was observed when Mx2 and Mx3 were combined, and this effect was intensified when the three isoforms were present in these cells. In contrast, the presence of more than one Mx isoform interfered with the antiviral activity against IPNV and VHSV showed by the Mx proteins expressed separately. Furthermore, Mx2 combined with Mx3, and the combination of the three Mx proteins exerted a negative synergistic effect against IPNV infection. Specifically, the viral titres were significantly higher in Mx expressing cells than in control cells. In the same way, in Mx1 and Mx2 expressing cells infected with VHSV the viral replication was alsoincreased. These results suggest the interaction between Mx isoforms, in which the expression level of each isoform might be an important factor, and support the idea of finely tuned mechanisms controlling the antiviral activity of Mx proteins. The authors want to thank Dr. C. P. Dopazo (University of Santiago de Compostela, Spain) and Dr. K. Way (CEFAS, Weymouth lab, UK) for supplying the viruses VHSV and ESV, respectively, used in this work.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Differential induction of the gilthead seabream Mx1, Mx2 and Mx3 promoters by IPNV and VHSV

Type I interferon (IFN I) system triggers specific signalling pathways leading to the activation of the innate immune defence of vertebrates against viral infections. The complex expression regulation of Interferon Stimulated Genes (ISGs) is responsible for the control of the IFN I response. Hence, one of the key issues in understanding virus-host interactions relies on the knowledge of the regulatory mechanisms governing ISGs expression. Among ISGs, the Mx proteins play a main role due to their direct antiviral activity. The study of Mx genes in the farmed fish gilthead seabream is especially interesting, since this species displays an unusually high natural resistance to viral diseases, and behaves as an asymptomatic carrier and/or reservoir of several viruses, such as infectious pancreatic necrosis virus (IPNV) and viral haemorrhagic septicaemia virus (VHSV), pathogenic to other fish species. Three independent Mx genes (Mx1, Mx2, and Mx3) have been identified in this species, showing the three proteins a wide spectrum of antiviral activity. The structure of the three promoters (pMx1, pMx2 and pMx3) has been disclosed, and their response to poly I:C characterized in RTG-2 cells, where a clear induction of the three promoters, although with some differences in the kinetics and magnitude of the response, was observed. To further analyse these promoters, the response of pMx1, pMx2 and pMx3 to two viral infections has been evaluated in the present study. For that purpose, RTG-2 cells were transiently transfected with plasmids containing each promoter driving the luciferase gene, and subsequently inoculated with either IPNV or VHSV. Although the three promoters were induced by IPNV and VHSV, several differences were recorded. In general, the response was stronger in cells inoculated with VHSV compared to IPNV-inoculated cells, and the fold induction was higher for pMx2. These results highlight the specific regulation that controls the activity of each promoter, and support the idea that a complex interaction between host cells, specific Mx promoters, and viruses, is the responsible of the final outcome of a viral infection, in terms of Mx induction. The authors want to thank Dr. C. P. Dopazo (University of Santiago de Compostela, Spain) for supplying the VHSV isolate used in this work.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Estudio Serológico y Molecular de Ehrlichia canis en Perros de una Comunidad del Estado Aragua, Venezuela

The aims of the study were to determine the prevalence of antibodies anti-E canis and the molecular detection of E. canis as well as to determine the species and level of tick infestations in dogs from a rural community in Aragua state, Venezuela. Blood samples from 110 domestic dogs were obtained and analyzed by Indirect Immunofluorescence (IFI) and Nested Polymerase Chain Reaction (PCR). The seroprevalence was 77.3% and the molecular detection was 45.2%. The percentage of dogs infested with ticks was 69%, mostly with Rhipicephalus sanguineus. The results showed that 80% (68/85) of seropositive dogs and 32% (8/25) of seronegative dogs were tick infested (OR=8.5, 95%, CI 3.19 to 22.6; p<0.00001).Los objetivos de esta investigación fueron determinar la prevalencia de anticuerpos anti-E. canis y la detección molecular de E. canis, así como determinar el nivel de infestación y especies de garrapatas en perros de una comunidad rural del estado Aragua, Venezuela. Se recolectaron muestras sanguíneas de 110 perros domésticos y fueron evaluadas por inmunofluorescencia indirecta (IFI) y por la técnica de reacción en cadena de la polimerasa anidada (PCR). La seroprevalencia resultó en 77.3% y la detección molecular fue de 45.2%. El porcentaje de perros infestados por garrapatas fue de 69%, identificándose mayormente a Riphicephalus sanguineus. Se determinó que 80% (68/85) de los perros seropositivos y el 32% (8/25) de los seronegativos estaban infestados por garrapatas (OR=8.5, IC 95%: 3.19-22.6; p<0.00001)

Innate and adaptive immune assessment at admission to predict clinical outcome in covid-19 patients

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27-CD28-, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27-CD28-, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease.Funding: This work was partially supported by the Cantabrian Government, grant number 2020UIC22-PUB-001, and by Instituto de Salud Carlos III, grant number COV20/00170

Aprendizaje flexible y personalizado para atender la diversidad en el aula, mediante la gamificación, a través del uso integrado de un sistema virtual de respuesta en el aula para dispositivos móviles con acceso a internet y una aplicación de screencasting

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de VeterinariaFALSEsubmitte

Estilos de consumo, actitudes hacia el dinero, y materialismo en adolescentes chilenos y ecuatorianos

En esta investigación se compara el efecto del modelo de consumo neoliberal en adolescentes, hombres y mujeres, de Quito (Ecuador) y Santiago (Chile). El objetivo es describir estilos de consumo, actitud hacia el dinero y materialismo en adolescentes de ambas ciudades y comparar de acuerdo a país de procedencia y género de los participantes. La muestra abarca 799 adolescentes de entre 14 y 17 años de edad, de Ecuador y Chile, la cual se obtuvo a través de un muestreo por conglomerado bietápico. Los resultados indican diferencias por género y ciudad respecto a la impulsividad en la compra, con los hombres de Quito como quienes tienen una actitud más impulsiva. Y en relación con la actitud hacia la compra se hallaron diferencias significativas por género, observando que los hombres son quienes le dan mayor estatus de poder y felicidad personal

"Escape Seminar": Escápate del seminario

Las "escape room" son juegos de equipo para "escapar" de una sala o una sala virtual. Esta sala está llena de desafíos que se deben superar para ganar (escapar) dentro de un límite de tiempo determinado. Debido a que la enseñanza tradicional está causando problemas en torno a la motivación y el compromiso, y muchos estudiantes la perciben como ineficaz y aburrida, el uso de juegos educativos es muy prometedor porque son una herramienta de enseñanza para mejorar las habilidades no cognitivas, como la resolución de problemas y la colaboración. y comunicación. Los juegos tienen un notable poder motivador debido al uso de una serie de mecanismos que alientan a las personas a participar en ellos, a menudo sin ninguna recompensa, solo por la satisfacción de jugar y la posibilidad de ganar. En el curso 2019-2020, hemos desarrollado actividades basadas en el concepto de la "escape room" en las asignaturas: "Ciencia y Análisis de agua y bebidas" del Grado en Ciencia y Tecnología de Alimentos, "Química Analítica I" y "Físico-Química Farmacéutica" del Grado de Farmacia y “Química” del Grado en Óptica y Optometría de la Universidad Complutense de Madrid. Para el desarrollo del proyecto, todas las características y el progreso de las diferentes fases del seminario de la "escape room" se informaron en el primer día de clase y a través de la plataforma del Campus Virtual. Los estudiantes se agruparon (5-7 personas / grupo) y nombraron un portavoz que fue responsable de responder los retos de la actividad. Al final de esta acción, los estudiantes respondieron voluntariamente a las encuestas Likert para evaluar sus implicaciones y su percepción sobre su aprendizaje, trabajo en equipo y si les gustó la actividad propuesta

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p <.001) and at 6 months (63.4% vs. 90.1%, p <.001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p =.001) and 6 months (p <.001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline