Phosphodiesterase-induced cAMP degradation restricts hepatitis B virus infection

Hepatitis B virus (HBV) entry into hepatocytes is mediated via a high affinity interaction between the preS1 glycoprotein and sodium/bile acid cotransporting polypeptide (NTCP). To date, in vitro model systems rely on high multiplicities of infection to achieve infection of cell lines overexpressing human NTCP. This study investigates a novel regulatory pathway for NTCP trafficking to the cell surface, induced by DMSO-mediated cellular differentiation. DMSO rapidly induces high cell surface expression of NTCP and results in increased susceptibility of cells to HBV infection. Additionally, DMSO treatment induces actin, as well as tubulin reshaping within the cells. We show that direct disruption of the actin and tubulin network directly enhances NTCP expression and the subsequent susceptibility of cells to HBV infection. DMSO induces these changes via alterations in the levels of cyclic (c)AMP, which participates in the observed actin rearrangements. Blocking of phosphodiesterases (PDEs), which degrade accumulated cAMP, had the same effect as DMSO differentiation and demonstrates that DMSO prevents phosphodiesterase-mediated cAMP degradation. This identifies adenylate cyclase as a novel target for blocking the entry of HBV via targeting the cell surface accumulation of NTCP

Sustainable Education: Using Social Networks in Education for Change

Creating societies of the future goes hand in hand with promoting sustainable education and, therefore, universities must train educators who, through their own professional development, put into practice methodologies that are active, participative, and focused on the overall development of their students. The use of methodologies like Design Thinking and the use of social networks generate learning dynamics that bring into play key competences in the development of dedicated future educators. In this study, 156 students from Education degrees at the University of Jaen analyze how the use of these methodologies supports the learning process in dimensions such as creativity, motivation, communication, and involvement in learning, among others. The results shows that all dimensions correlate positively, and that the benefits derived from the use of these methodologies are perceived by students as greater than the effort required to put them into practice

AI Researchers, Video Games Are Your Friends!

If you are an artificial intelligence researcher, you should look to video games as ideal testbeds for the work you do. If you are a video game developer, you should look to AI for the technology that makes completely new types of games possible. This chapter lays out the case for both of these propositions. It asks the question "what can video games do for AI", and discusses how in particular general video game playing is the ideal testbed for artificial general intelligence research. It then asks the question "what can AI do for video games", and lays out a vision for what video games might look like if we had significantly more advanced AI at our disposal. The chapter is based on my keynote at IJCCI 2015, and is written in an attempt to be accessible to a broad audience.Comment: in Studies in Computational Intelligence Studies in Computational Intelligence, Volume 669 2017. Springe

ESTUDIO DEL DA 1O HEP\uc1TICO DE UNA DOSIS ALTA DE OXITETRACICLINA EN RATONES (MUS MUSCULUS) HEMBRAS PRE 1ADAS

Entre los antibi\uf3ticos que pueden causar h\uedgado graso (HG) se encuentra la oxitetraciclina (OT). Este estudio tuvo como objetivo determinar el da\uf1o hep\ue1tico de una dosis alta de OT en ratones hembras pre\uf1adas y su asociaci\uf3n con el estr\ue9s oxidativo (EO). Treinta ratones hembras NMRI distribuidas en tres grupos de diez animales: D\ueda 0 no pre\uf1ado, al Parto, mantenido hasta el nacimiento, al Destete, mantenido hasta el destete. En todos, la mitad fue inyectada i.p. con dosis \ufanica de 100 mg/kg de OT, grupo experimental. Los resultados son la media\ub1ES; la significaci\uf3n estad\uedstica se obtuvo mediante "t" Student. El HG se evalu\uf3 por histolog\ueda y por la concentraci\uf3n de triglic\ue9ridos hep\ue1ticos. Como par\ue1metros de EO, se determin\uf3 por espectrofotometr\ueda la concentraci\uf3n hep\ue1tica de dienos conjugados (DC) y de MDA. La funcionalidad hep\ue1tica fue evaluada por la actividad plasm\ue1tica de las aminotransferasas ALT y AST mediante kits comerciales. Los resultados mostraron que una dosis alta de OT, a las 24 horas, en ratones hembras no pre\uf1adas (grupo D\ueda 0) elev\uf3 los triglic\ue9ridos hep\ue1ticos, acompa\uf1ada de hepatoesteatosis e incremento plasm\ue1tico de ALT y AST. En ellos se constat\uf3 EO, evidenciado por alta concentraci\uf3n de DC y MDA. Al parto las hembras pre\uf1adas experimentales, no presentaron modificaci\uf3n de los par\ue1metros descritos en el grupo D\ueda 0, poniendo en evidencia que a los 21 d\uedas despu\ue9s de la administraci\uf3n de una dosis alta de OT, no se mantuvo el efecto del anibi\uf3tico, un resultado similar fue obtenido en las hembras al momento del destete. Palabras clave: oxitetraciclina, da\uf1o hep\ue1tico, pre\uf1ez. ABSTRACT Among the antibiotics that can cause fatty liver (HG) is oxytetracycline (OT). This study aimed to determine the hepatic damage of a high dose of OT in pregnant female mice and its association with oxidative stress (OE). 30 NMRI female mice distributed in three groups of 10 animals: Day 0 not pregnant, to Parturition, maintained until delivery, to Weaning, maintained until weaning. In all, half was injected i.p. with a single dose of 100 mg/kg OT, experimental group. The results are the mean\ub1SE, the statistical significance was obtained by Student\ub4s t-test. HG was evaluated by histology and by the concentration of hepatic triglycerides. As OE parameters, the hepatic concentration of conjugated dienes (DC) and MDA was determined by spectrophotometry. Liver function was assessed by the plasma activity of the aminotransferases ALT and AST by commercial kits. The results showed that a high dose of OT, at 24 hours in non-pregnant female mice (Day 0 group) elevated the hepatic triglycerides, accompanied by hepatoesteatosis and increased plasma ALT and AST. OE was found in them, evidenced by high concentration of DC and MDA. At delivery, the experimental pregnant females did not present any modification of the parameters described in the Day 0 group, evidencing that at 21 days after the administration of a high OT dose, the effect of the anibiotic was not maintained, a similar result was obtained in the females at the time of weaning. Key words: Oxytetracycline, hepatic damage, pregnancy. <br

Extinction of Hepatitis C Virus by Ribavirin in Hepatoma Cells Involves Lethal Mutagenesis

Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV

Estudio del efecto solvatocrómico en derivados fenólicos naturales

Se describen las características espectrofluorimétricas de dos derivados de quercetina aislados de las hojas deFlaveria bidentis, un derivado de 6-prenilpinocembrina, aislado de las raíces de Dalea elegans y un compuesto deestructura antraquinónica aislado de las hojas de Heterophyllaea pustulata. Todos ellos presentan espectros deabsorción con máximos en la región UV-visible acordes con los grupos cromóforos presentes en su estructura. Loscuatro compuestos estudiados presentan fluorescencia nativa. La posición de los máximos de emisión de fluorescenciase modifica en función del disolvente. Los desplazamientos producidos están relacionados con el diferente gradode solvatación de las moléculas en estado excitado según la polaridad del disolvente. La adición de ácidos mineralesprovoca desplazamientos en los máximos de fluorescencia concordantes con los ya descritos para compuestos deestructura similar. Estas modificaciones espectrales tienen un gran interés analítico desde el punto de vista de laidentificación y caracterización de productos naturales de estructura fenólica

Análisis e influencia de los sistemas de referencia en la cinemática del hombro

The shoulder is one of the most complex systems in the human body. To know how its work is essential to understand the biomechanics of the body. The purpose of this study was to analyze the influence of Local Coordinate Systems in the kinematic analysis of GlenoHumeral joint. The motion tracking was performed using passive sensors attached to pins. Trabecular pins were placed on the shoulder and scapula. The data processing was performed using the free open software pyFormex. The joint displacements were determined by two different variants of Coordinate Systems, being detected a difference from 2 to12 degrees

Seminar Users in the Arabic Twitter Sphere

We introduce the notion of "seminar users", who are social media users engaged in propaganda in support of a political entity. We develop a framework that can identify such users with 84.4% precision and 76.1% recall. While our dataset is from the Arab region, omitting language-specific features has only a minor impact on classification performance, and thus, our approach could work for detecting seminar users in other parts of the world and in other languages. We further explored a controversial political topic to observe the prevalence and potential potency of such users. In our case study, we found that 25% of the users engaged in the topic are in fact seminar users and their tweets make nearly a third of the on-topic tweets. Moreover, they are often successful in affecting mainstream discourse with coordinated hashtag campaigns.Comment: to appear in SocInfo 201