Cross-linking mass spectrometry uncovers protein interactions and functional assemblies in synaptic vesicle membranes

Synaptic vesicles are storage organelles for neurotransmitters. They pass through a trafficking cycle and fuse with the pre-synaptic membrane when an action potential arrives at the nerve terminal. While molecular components and biophysical parameters of synaptic vesicles have been determined, our knowledge on the protein interactions in their membranes is limited. Here, we apply cross-linking mass spectrometry to study interactions of synaptic vesicle proteins in an unbiased approach without the need for specific antibodies or detergent-solubilisation. Our large-scale analysis delivers a protein network of vesicle subpopulations and functional assemblies including an active and an inactive conformation of the vesicular ATPase complex as well as non-conventional arrangements of the luminal loops of SV2A, Synaptophysin and structurally related proteins. Based on this network, we specifically target Synaptobrevin-2, which connects with many proteins, in different approaches. Our results allow distinction of interactions caused by ‘crowding’ in the vesicle membrane from stable interaction modules.Projekt DEA

An overview of the synaptic vesicle lipid composition

This work was funded by a Ramon y Cajal grant to A.P-L. (RYC2018-023837-I) and by a grant from the National Institutes of Health to R.J. (P01 GM072694) .Chemical neurotransmission is the major mechanism of neuronal communication. Neurotransmitters are released from secretory organelles, the synaptic vesicles (SVs) via exocytosis into the synaptic cleft. Fusion of SVs with the presynaptic plasma membrane is balanced by endocytosis, thus maintaining the presynaptic membrane at steadystate levels. The protein machineries responsible for exo-and endocytosis have been extensively investigated. In contrast, less is known about the role of lipids in synaptic transmission and how the lipid composition of SVs is affected by dynamic exo-endocytotic cycling. Here we summarize the current knowledge about the composition, organization, and function of SV membrane lipids. We also cover lipid biogenesis and maintenance during the synaptic vesicle cycle.Spanish Government RYC2018-023837-IUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA P01 GM07269

De la extremaunción a la unción de los enfermos. Un cambio litúrgico en la Iglesia Católica

The objective of this work is to analyze briefly a liturgical change, which arose as part of the multiple reforms that were carried out during the Second Vatican Council. This analysis is the substitution from the ritual of extreme unction to the anointing of the sick people, focused on the healing of the believers of the Catholic Church, and in what way this religious practice is structured, which even in our present it is a significant part in the multiple rituals that characterize thereligion with more presence-although in decay-in our country.El objetivo de este trabajo es analizar brevemente un cambio litúrgico que se suscitó como parte de las múltiples reformas que se llevaron a cabo durante el Concilio Vaticano II. El análisis en cuestión es el reemplazo del ritual de la extremaunción por el de la unción de los enfermos, el cual se enfoca a la sanaciónde los creyentes de la Iglesia Católica. Asimismo, se estudia de qué manera está estructurada dicha práctica religiosa, la cual hasta nuestros días forma parte significativa dentro de los múltiples rituales que caracterizan a la religión con más presencia –aunque en decadencia– en nuestro país

Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2

The transient outward potassium current (Itof) is generated by the activation of KV4 channels assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 channels. CHO cells were transiently transfected with cDNAs codifying for different proteins (KV4.3/KChIP2, KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using the whole-cell patch-clamp technique. IQM-266 decreased the maximum peak of KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 currents, slowing their time course of inactivation in a concentration-, voltage-, time- and use-dependent manner. IQM-266 produced an increase in the charge in KV4.3/KChIP2 channels that was intensified when DPP6 was present and abolished in the presence of KCNE2. IQM-266 induced an activation unblocking effect during the application of trains of pulses to cells expressing KV4.3/KChIP2 and KV4.3/KChIP2/KCNE2, but not in KV4.3/KChIP2/DPP6 channels. Overall, all these results are consistent with a preferential IQM-266 binding to an active closed state of Kv4.3/KChIP2 and Kv4.3/KChIP2/KCNE2 channels, whereas in the presence of DPP6, IQM-266 binds preferentially to an inactivated state. In conclusion, DPP6 and KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266.MCIN/AEI SAF2016-75021-R RTI2018-097189-B-C22 BIO2017-89523-R PID2019-104366RB-C21 PID2019-104366RB-C22 PID2020-114256RB-I00 PID2020-119805RB-I00 BES-2017-080184 BES-2010-036573 PRE2018-083280 RYC2018-023837-IERDF A way of making Europe SAF2016-75021-R RTI2018-097189-B-C22 BIO2017-89523-RFEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento A-FQM-386-UGR20Instituto de Salud Carlos III CIBERCV CB/11/00222Consejo Superior de Investigaciones Cientificas PIE202180E073 PIE201820E104 2019AEP148ESF Investing in your future BES-2017-080184 BES-2010-036573 PRE2018-083280 RYC2018-023837-IInstituto de Salud Carlos IIISpanish GovernmentEuropean Commission FPU17/0273

Evaluation of quality in higher education: content validity

El cambio de perspectiva sobre la educación superior en España ha posibilitado el desarrollo de nuevos marcos jurídicos que dan mayor autonomía a las universidades. Al mismo tiempo los gobiernos, tanto nacional como autonómicos, necesitan recabar información sobre cómo se gestiona dicha autonomía. Esta situación ha impulsado la necesidad de definir el constructo de calidad en la universidad y de generar procedimientos adecuados para su evaluación. El objetivo de este trabajo es por una parte, justificar cómo los sistemas de indicadores suponen una posible solución a esta problemática, y por otra analizar empíricamente la validez de contenido de un conjunto de indicadores seleccionados a partir de una revisión bibliográfica. El proceso seguido en el estudio empírico fue el siguiente: se seleccionaron indicadores que hacen referencia a distintos aspectos relacionados con la educación superior (enseñanza, investigación y gestión); se consultó a un grupo de expertos sobre la adecuación de dichos indicadores y se utilizó el índice de Osterlind (1989) como una forma de operativizar el consenso entre los expertos respecto a la idoneidad de los indicadores seleccionados para evaluar la calidad universitaria. Se presentan los indicadores obtenidos en el análisis como una alternativa posible para el estudio de la calidad universitariaThe new conception of higher education in Spanish society and in its national, regional and local governments has generated laws that give more independence to universities. Because of this situation, governments need information about how universities use that independence. This context has stressed the need of defining the construct of quality in higher education and the difficulty that implementing an appropriate evaluation procedure entails. This paper has two aims: first, to justify that systems of indicators are a plausible alternative to both problems, and second, to study the content validity of a group of indicators chosen from the literature. We have carried out the following process in the empirical study: we selected some indicators related to higher education (about teaching, research, and services); we consulted experts about the congruence of these indicators, and finally we used the Osterlind´s index (1989) to operationalize the consensus between experts about their judgments. We describe the quality indicators obtained in this analysis as a possible alternative to study quality in higher education

Assessment of the effects of digital educational material on executive function performance

The Learning Analytics system of the Smile and Learn platform recorded the students'use during class. According to the usage analysis, the results obtained show preference of using activities from Logic and Spatial worlds. In the external analysis of the effect of the learning material, the results record a significant effect using activities in Logic and Spatial worlds with the Gray Trails task, which involves spatial perception, processing speed, and working memory, among others. A second analysis to contrast the results with a post hoc design approaches relationships among executive functions as involved in tasks like Gray Trails, Interference, and Ring Tasks within the usage of Spatial and Logic activities. The need for further research to improve these materials for enhanced learning and the extrapolation of training from executive functions to other tasks is discussed. Likewise, limitations of the implementation and design of these materials are pointed out.This study is part of the project IND2017/SOC-7874 for assessment and improve the digital material design, funded by the Community of Madrid by 'Industrial Ph.D' grants

An Exploratory Analysis of the Implementation and Use of an Intelligent Platform for Learning in Primary Education

Smile and Learn is an intelligent platform with more than 4500 educational activities for children aged 3–12. The digital material developed covers all courses of primary education and most of the subjects with the different topic-related worlds with activities in the field of logics and mathematics, science, linguistics and tales, visual-spatial and cognitive skills, emotional intelligence, arts, and multiplayer games. This kind of material supports active learning and new pedagogical models for teachers to use in their lessons. The purpose of this paper is to explore the usage of the platform in three pilot groups schools from different regions of Spain, outlining future directions in the design of such digital materials. Usage is assessed via descriptive analysis and variance analysis, with data collected from users interacting with the intelligent platform. The results show a high use of STEM (Science, Technology, Engineering and Maths) activities among all the activities that could be chosen. Cross-curricular activities are also used. Continuation in the development of such materials is concluded necessary, focusing integration of different fields, accentuating games over quizzes, and the value of teacher training for improving their use in schools

Impulsivity and the Experience of Desire in the Choice of Erotic Stimuli

(1) Background: the relationship between erotic desire and personality factors is still relatively understudied. (2) Objective: to study the influence of the experience of desire, as well as impulsivity in the choice of videos, as the behavioral variable in the experimental trial. (2) Method: the sample consisted of 48 adult subjects, who took part in an experimental study that involved watching videos. (3) Results: the linear regression analysis revealed that the behavior involved in choosing videos is predicted by the sexual desire felt at the time of the trial, and not by stable personality factors, such as impulsivity or general self-report levels of sexual desire. (4) Conclusion: it is observed that the specific moment or situation and the behavior have a bigger impact on the erotic desire experienced at the time of the test than certain personality traits, as well as the previous and habitual levels of erotic desire of which an individual reports

Vía aérea difícil en pediatría: signos predictores. Artículo de revisión. Difficult airway in pediatrics. Predicting signs

El manejo de la Vía Aérea es la A del ABC de la medicina moderna y representa un reto para el anestesiólogo experto, y aún más para el que se encuentra en entrenamiento. Una intubación difícil no anticipada es una emergencia médica, si no es tratada con rapidez y de forma apropiada, puede condicionar problemas serios y hasta la muerte del paciente. En el presente artículo se hace una revisión del diagnóstico precoz de esta entidad, mediante signos predictores, teniendo en cuenta algunas de las características principales de la vía aérea del niño que la diferencian del adulto. Palabras clave: predictores, vía aérea, intubación endotraqueal ABSTRACT The management of the airway is the A in the ABC of current medicine, and represents a challenge for an expert in anestesiology, and much more for those in the training process. An anticipated difficult intubation is a medical emergency which must be treated rapidly and properly because it can result in serious problems and lead to death. In this article a review of the early diagnosis of this entity through predicting signs , considering some main features at the child airway which are different from the adult's was carried out. Key words: PREDICTING SIGNS, AIRWAY, ENDOTRACHEAL INTUBATION