Regulation of endoplasmic reticulum-associated protein degradation (ERAD) by ubiquitin

Quality control of protein folding inside the endoplasmic reticulum (ER) includes chaperone-mediated assistance in folding and the selective targeting of terminally misfolded species to a pathway called ER-associated protein degradation, or simply ERAD. Once selected for ERAD, substrates will be transported (back) into the cytosol, a step called retrotranslocation. Although still ill defined, retrotranslocation likely involves a protein conducting channel that is in part formed by specific membrane-embedded E3 ubiquitin ligases. Early during retrotranslocation, reversible self-ubiquitination of these ligases is thought to aid in initiation of substrate transfer across the membrane. Once being at least partially exposed to the cytosol, substrates will become ubiquitinated on the cytosolic side of the ER membrane by the same E3 ubiquitin ligases. Ubiquitin on substrates was originally thought to be a permanent modification that (1) promotes late steps of retrotranslocation by recruiting the energy-providing ATPase Cdc48p/p97 via binding to its associated adaptor proteins and that (2) serves to target substrates to the proteasome. Recently it became evident, however, that the poly-ubiquitin chains (PUCs) on ERAD substrates are often subject to extensive remodeling, or processing, at several stages during ERAD. This review recapitulates the current knowledge and recent findings about PUC processing on ERAD substrates and ubiquitination of ERAD machinery components and discusses their functional consequences

An ER-Localized SNARE Protein Is Exported in Specific COPII Vesicles for Autophagosome Biogenesis

The de novo formation of autophagosomes for the targeting of cytosolic material to the vacuole/lysosome is upregulated upon starvation. How autophagosomes acquire membranes remains still unclear. Here, we report that, in yeast, the endoplasmic reticulum (ER)-localized Qa/t-SNARE Ufe1 has a role in autophagy. During starvation, Ufe1 is increasingly exported from the ER and targeted to intracellular sites that contain the autophagy markers Atg8 and Atg9. In addition, Ufe1 interacts with non-ER SNARE proteins implicated in autophagosome formation. Loss of Ufe1 function impairs autophagy and results in fewer and smaller autophagosomes. Unlike conventional cargo, the ER export of Ufe1 is significantly reduced in sec23-1 cells, which affects the coat protein (COP)II complex, already at the permissive temperature. Under the same conditions, sec23-1 cells are hypersensitive to starvation and deficient in autophagy. Our data suggest that ER membranes containing Ufe1 are delivered to sites of autophagosome formation in specific COPII vesicles.EMBO short-term fellowship (EMBO ASTF) 293-2015Spanish, Ministry of ScienceSpanish Government BFU2009-07290Ramon y Cajal program Spanish Government BFU2014-59309-

Complicaciones asociadas a enfermedad por reflujo gastroesofágico en pacientes de 1 a 12 años, tratados en Consulta Externa del Hospital de Niños Benjamín Bloom desde 01 de Enero 2014 al 31 de Diciembre 2018.

El reflujo gastroesofágico es una alteración gastrointestinal que puede ocurrir en el 40%-70% de los lactantes sanos y que generalmente resuelve al año de edad. (1). Se estima que 10 a 20% de estos pacientes desarrollan enfermedad por reflujo gastroesofágico, pudiendo ocasionar complicaciones esofágicas o extraesofágicas, que afectan la vida de los infantes (2). Objetivo: Describir la prevalencia de complicaciones asociadas a enfermedad por Reflujo Gastroesofágico en la población pediátrica con edades entre 1 y 12 años, atendida en el servicio de gastroenterología, desde enero de 2014 hasta diciembre de 2018. Material y métodos: Se realizó un estudio de tipo descriptivo, transversal y retrospectivo. Con un universo de 1149 pacientes. Se tomó una muestra representativa de 163 pacientes, divididos en 2 grupos según diagnostico establecido en la clasificación Internacional de enfermedades CIE-10: Reflujo gastroesofágico con esofagitis (K21.9) o sin esofagitis (K21.0) Los datos encontrados se presentan en tablas y gráficos de frecuencias, se analizaron usando estadística descriptiva. Resultados: Los lactantes de 12 y 36 meses de edad, son el grupo de edad con mayor proporción de casos, sin esofagitis 60% y 53% con esofagitis, La mediana se encuentra 34 meses (2.8 años) para los pacientes con esofagitis y en 31 (2.5 años) meses para los pacientes sin esofagitis. El sexo femenino es el más afectado con una proporción de 1.17 - 1.22 a 1 con el sexo masculino. El 22% de pacientes presenta alguna enfermedad crónica concomitante, siendo las enfermedades neurológicas las más frecuentes. Los signos y síntomas clínicos más frecuentes fueron: rechazo al alimento, regurgitación recurrente, y dolor torácico o pirosis. El método diagnóstico más usado es la valoración clínica. Las pruebas diagnósticas más usadas son: la endoscopia y el estudio radiológico. El medicamento más utilizado es ranitidina (77%). La prescripción de procinéticos es de un 59% de pacientes. El 22% de los pacientes presentan complicaciones, siendo estas: anemia y falla de medro y síndrome de tos por reflujo

A probability-based multimetric routing protocol for vehicular ad hoc networks in urban scenarios

Vehicular Ad hoc Networks have received considerable attention in recent years and are considered as one of the most promising ad-hoc network technologies for intelligent transport systems. Vehicular Ad hoc Networks have special requirements and unique characteristics (e.g., special mobility patterns, short life links, rapid topology changes) which make the design of suitable routing protocols, a challenge. Consequently, an efficient routing protocol that fits with VANETs’ requirements and characteristics is a crucial task to obtain a good performance in terms of average percentage of packet losses and average end-to-end packet delay. To attain this goal, we propose a novel probabilistic multimetric routing protocol (ProMRP) that is specially designed for VANETs. ProMRP estimates the probability for each neighbor of the node currently carrying the packet, to successfully deliver a packet to destination. This probability is computed based on four designed metrics: distance to destination, node’s position, available bandwidth and nodes’ density. Furthermore, an improved version of ProMRP called EProMRP is also proposed. EProMRP includes an algorithm that accurately estimates the current position of nodes in the moment of sending the packet instead of using the last updated position obtained from the previous beacon message. Simulations are carried out in a realistic urban scenario using OMNeT++/VEINS/SUMO, including real maps from the OpenStreetMaps platform. Simulation results show a better performance of ProMRP and EProMRP compared to recent similar proposals found in the literature in terms of packet losses and end-to-end packet delay, for different vehicles’ densities.Peer ReviewedPostprint (published version

A traffic-aware electric vehicle charging management system for smart cities

© . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The expected increase in the number of electric vehicles (EVs) in the coming years will contribute to reducing CO2 pollution in our cities. Currently, EVs' users may suffer from distress due to long charging service times and overloaded charging stations (CSs). Critical traffic conditions (e.g., traffic jams) affect EVs' trip time (TT) towards CSs and thus influence the total trip duration. With this concern, Intelligent transport systems (ITS) and more specifically connected vehicle technologies, can leverage an efficient real-time EV charging service by jointly considering CSs status and traffic conditions in the city. In this work, we propose a scheme to manage EVs' charging planning, focusing on the selection of a CS for the energy-requiring EV. The proposed scheme considers anticipated charging slots reservations performed through a vehicular ad hoc network (VANET), which has been regarded as a cost-efficient communication framework. In specific, we consider two aspects: 1) the EV's total trip time towards its destination considering an intermediate charging at each candidate CS, and 2) the communication delay of the VANET routing protocol. First, in order to estimate the EV's total trip time, our CS selection scheme takes into account the average road speed, traffic lights, and route distance, along the path of the EV. The optimal CS that produces the minimum total charging service time (including the TT) is suggested to that energy-requiring EV. Then, we introduce two communication modes based on geographical routing protocols for VANETs to attain an anticipated charging slot reservation. Simulation results show that with our charging scheme EVs' charging service time is reduced and more EVs are successfully charged.Peer ReviewedPostprint (author's final draft

Large-scale simulations manager tool for OMNeT ++: expediting simulations and post-processing analysis

Usually, simulations are the first approach to evaluate wireless and mobile networks due to the difficulties involved in deploying real test scenarios. Working with simulations, testing, and validating the target network model often requires a large number of simulation runs. Consequently, there are a significant amount of outcomes to be analyzed to finally plot results. One of the most extensively used simulators for wireless and mobile networks is OMNeT++. This simulation environment provides useful tools to automate the execution of simulation campaigns, yet single-scenario simulations are also supported where the assignation of resources (i.e., CPUs) has to be declared manually. However, conducting a large number of simulations is still cumbersome and can be improved to make it easier, faster, and more comfortable to analyze. In this work, we propose a large-scale simulations framework called simulations manager for OMNeT ++ (SMO). SMO allows OMNeT++ users to quickly and easily execute large-scale network simulations, hiding the tedious process of conducting big simulation campaigns. Our framework automates simulations executions, resources assignment, and post-simulation data analysis through the use of Python’s wide established statistical analysis tools. Besides, our tool is flexible and easy to adapt to many different network scenarios. Our framework is accompanied by a command-line environment allowing a fast and easy manipulation that allows users to significantly reduce the total processing time to carry out large sets of simulations about 25% of the original time. Our code and its documentation are publicly available at GitHub and on our website.This work was supported by the Spanish Government through the Research Project sMArt Grid Using Open Source Intelligence (MAGOS) under Grant TEC2017-84197-C4-3-R. The work of Pablo Andrés Barbecho Bautista was supported by a grant from the Secretaría Nacional de Educación Superior, Ciencia y Tecnología (SENESCYT). The work of Leticia Lemus CÁrdenas was supported by a Ph.D. grant from the Academic Coordination of the University of Guadalajara, Mexico.Peer ReviewedPostprint (published version

El entrenamiento autógeno de Schultz y la autoconfianza en el JUDOKA guatemalteco.

Determina que el entrenamiento autógeno es una técnica psicoterapéutica basada en la concentración pasiva en sensaciones físicas. Constituye la base de los métodos de psicoterapia autógena. La investigación se realizó en la Federación Nacional de Judo de Guatemala integrante del programa Sideporte. La muestra estuvo conformada por 18 judokas, 8 de sexo femenino y 10 masculinos, comprendidos entre los 14 a 18 años de edad. Para recolectar datos se utilizaron las técnicas siguientes: Test Par P1, entrevista estructurada y hoja de auto informe. Analiza e interpreta los resultados y concluye que, la ejecución de un programa de implementación en el entrenamiento autógeno de Schultz incide positivamente en la autoconfianza del judoka, de la Federación Nacional de Judo de Guatemala integrante del programa Sideporte

Education at the crossroads: tensions and inequalities in the life courses of secondary school teachers during the pandemic

Esta investigación se inscribe en el proyecto PISAC COVID 19 0014 “Heterogeneidad estructural y desigualdades persistentes en Argentina 2020-2021: análisis de las reconfiguraciones provocadas por la pandemia COVID-19 sobre las políticas nacionales-provinciales-locales y su impacto en la estructura y la dinámica socio-ocupacional. Un abordaje mixto y regional”, que recibió financiamiento de la Agencia I+D+I. Nuestro equipo de trabajo analizó las transformaciones que la pandemia del COVID 19 trajo sobre distintas comunidades educativas en el Gran La Plata, provincia de Buenos Aires. Este artículo aborda las transiciones laborales de docentes de diferentes escuelas secundarias, con el objeto de conocer en profundidad los cambios que debieron introducir en su práctica docente en el pasaje de la prepandemia a la pandemia, atendiendo especialmente a las distintas posibilidades que tuvieron de acuerdo a las características de la población estudiantil de las diferentes comunidades educativas en las que trabajaban.En particular, en el marco de la investigación cualitativa, realizamos 12 entrevistas biográficas semi-estructuradas a docentes y directivos/as que pertenecían a tres instituciones educativas estatales.Los principales hallazgos nos permiten sostener que la pandemia significó para los/las docentes el advenimiento de dos encrucijadas en su práctica docente durante el ASPO: por un lado, debieron desarrollar habilidades y adquirir saberes para usar las tecnologías digitales para enseñar a distancia y en condiciones desiguales en términos de conectividad por parte de los/as alumnos/as; por otro lado, tuvieron que construir un vínculo pedagógico a distancia y virtualmente, generando cercanía sin comprometer la privacidad (algo no siempre logrado), y establecer fronteras institucionales, espaciales y temporales desde la intimidad de su hogar y con la presencia ubicua de dispositivos, plataformas y conexiones. Durante el momento del DISPO las transiciones docentes evidenciaron una vuelta a la normalidad prepandemia, reencauzando su trayectoria laboral, aunque con nuevos saberes vinculados a las TD que pudieron continuar utilizando en el contexto áulico.In this paper we present findings from a recently finished project funded by Agencia I+D+I .PISAC COVID 19 0014, Heterogeneidad estructural y desigualdades persistentes en Argentina 2020-2021: análisis de las reconfiguraciones provocadas por la pandemia COVID-19 sobre las políticas nacionales-provinciales-locales y su impacto en la estructura y la dinámica socio-ocupacional. Un abordaje mixto y regional”.Within this project, our research group analyzed changes in educational community relationships and transformations in teaching practices resulting from the COVID-19 pandemic and the schools shut in Gran La Plata (Buenos Aires province, Argentina). In this paper we analyze 12 in depth interviews with secondary school teachers and school principals from 3 different state schools. We focus on teachers' transitions to teaching remotely and on digital platforms from home and, in some schools, their strategies to cope with students’ lack of digital devices and Internet connectivity.Our main findings suggest that teaching during the first stages of the pandemic -ASPO- was highly disruptive and challenging for secondary school teachers and that they had two face crossroads. On one hand, they had to rapidly develop new teaching skills that involve an intensive use of the Internet, platforms and digital devices. While learning how to teach remotely and from home, they had also to plan school lessons considering unequal connectivity scenarios among students. On the other hand, secondary school teachers had to build relationships with students remotely, in most cases from scratch, in a completely new virtual school setting and without compromising privacy. At the same time, teachers had to develop strategies to deal with everyday life, and teaching at the same place.As the pandemic unfolded and schools opened again in June 2021, teaching practices and educational community relationships started going back to pre COVID 19 normality.Facultad de Humanidades y Ciencias de la Educació

Limited ER quality control for GPI-anchored proteins

Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevantEspaña, Ministerio de Ciencia e Innovación BFU2014-59309-PEspaña, Ministerio de Ciencia e Innovación BFU2009-07290España, Junta de Andalucía P09-CVI-450