The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner

All cells and organisms exhibit stress-coping mechanisms to ensure survival. Cytoplasmic protein-RNA assemblies termed stress granules are increasingly recognized to promote cellular survival under stress. Thus, they might represent tumor vulnerabilities that are currently poorly explored. The translation-inhibitory eIF2α kinases are established as main drivers of stress granule assembly. Using a systems approach, we identify the translation enhancers PI3K and MAPK/p38 as pro-stress-granule-kinases. They act through the metabolic master regulator mammalian target of rapamycin complex 1 (mTORC1) to promote stress granule assembly. When highly active, PI3K is the main driver of stress granules; however, the impact of p38 becomes apparent as PI3K activity declines. PI3K and p38 thus act in a hierarchical manner to drive mTORC1 activity and stress granule assembly. Of note, this signaling hierarchy is also present in human breast cancer tissue. Importantly, only the recognition of the PI3K-p38 hierarchy under stress enabled the discovery of p38’s role in stress granule formation. In summary, we assign a new pro-survival function to the key oncogenic kinases PI3K and p38, as they hierarchically promote stress granule formation

Desarrollo de un sistema informático para gestionar la información de la seguridad de los puestos de trabajo de la ESPOCH, aplicando tecnología responsive.

En este trabajo de titulación se desarrolló un sistema informático para gestionar la información de la seguridad de los puestos de trabajo de la Escuela Superior Politécnica de Chimborazo (ESPOCH), aplicando tecnología responsive, lo cual automatizó y agilizó el proceso de control de normas de seguridad por puesto de trabajo. Se utilizaron técnicas como, encuesta y observación para lograr identificar problemas y necesidades de la Unidad de Salud en el Trabajo, para el desarrollo del sistema informático se utilizó la metodología ágil Scrum por proporcionar etapas para el ciclo de vida del software, permitiendo una mayor probabilidad de éxito del proyecto, al ir cumpliendo de manera correcta cada fase, además de estar sujeto a cambios e incluir constantemente al cliente. Para el desarrollo del software se utilizaron lenguajes de programación como JAVA, JavaScript para la lógica de programación , HTML,CSS, Boostrap, Foundation para el maquetado de la interfaz web, PostgreSql como el gestor de base de datos para el almacenamiento de la información , Servicios Res full, Ide Netbeans 8.0.2 como entorno de desarrollo integrado, para validar la eficiencia se utilizó el estándar ISO/IEC 9126 del cual se tomó la sub característica tiempo de respuesta y utilización de recursos. Mediante la aplicación de la metodología se desarrollaron, un total de 5 historias técnicas,15 historias de usuario,33 tareas de ingeniería y 52 pruebas de aceptación. Pruebas exitosas, que se hicieron utilizando un servidor proporcionado por la Dirección de Tecnologías de la Información y la Comunicación (DTIC). En conclusión, se determinó que, mediante la generación de un documento a través del sistema informático, con la información más relevante de las normas de seguridad, accidentes e incidentes laborales, por cada puesto de trabajo se tiene un mejor control y así se mejora la calidad de trabajo de los empleados.In this degree work, a computer system was developed to manage the information on the security of the jobs of the Higher Polytechnic School of Chimborazo, applying responsive technology, which automated and streamlined the process of control of safety regulations by post work. Techniques such as survey and observation were used to identify problems and needs of the Health Unit at Work. For the development of the computer system, the Agile Scrum methodology was used to provide stages for the software life cycle; allowing a higher probability of success of the project, to be fulfilling each phase correctly, in addition to being subject to changes and continuously include the client. For the development of the software, programming languages such as JAVA, Javascript for programming logic, HTML, CSS, Bootstrap, Foundation were used for the layout of the web interface. PostgreSQL as the database manager for the storage of information, Res full services, Ide NetBeans 8.0.2 as an integrated development environment, to validate the efficiency the ISO / IEC 9126 standard was used, from which the sub-characteristic response time and resource utilization were taken. Through the application of the methodology, a total of 5 technical stories, 15 user stories, 33 engineering tasks, and 52 acceptance tests were developed. Successful tests that were made using a server provided by the Directorate of Information and Communication Technologies. In conclusion, it was determined that by generating a document through the computer system, with the most relevant information of safety regulations, accidents and labor incidents, for each job you have better control and thus the quality is improved of employees' work