Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells

Carotid body glomus cells release transmitters in response to hypoxia due to the increase of excitability resulting from inhibition of O2 -regulated K+ channels. However, the mechanisms involved in the detection of changes of O2 tension are unknown. We have studied the interaction between glomus cell O2 sensitivity and inhibition of the mitochondrial electron transport chain (ETC) in a carotid body thin slice preparation in which catecholamine release from intact single glomus cells can be monitored by amperometry. Inhibition of the mitochondrial ETC at proximal and distal complexes induces external Ca2+-dependent catecholamine secretion. At saturating concentration of the ETC inhibitors, the cellular response to hypoxia is maintained. However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dose-dependent manner. The effect of rotenone is mimicked by 1-methyl-4-phenylpyridinium ion(MPP+), an agent that binds to the same site as rotenone, but not by complex I inhibitors acting on different sites. In addition, the effect of rotenone is not prevented by incubation of the cells with succinate, a substrate of complex II. These data strongly suggest that sensitivity to hypoxia of carotid body glomus cells is not linked in a simple way to mitochondrial electron flow and that a rotenone (and MPP+)-sensitive molecule critically participates in acute oxygen sensing in the carotid body.Ministerio de Ciencia y Tecnología 1FD97–161

School autonomy in Basic Education (1982-2014): A state of the question from the supranational perspective

En este artículo presentamos un panorama general sobre los principales enfoques epistémicos en la investigación sobre política educativa en el mundo, centrado de modo específico en las contribuciones hacia la producción de conocimiento de la autonomía de gestión y su relación con la Agenda Globalmente Estructurada para la Educación (AGEE), con la intención de describir el posicionamiento de una política pública en su dimensión supranacional y nacional, para lo cual se adopta el enfoque metodológico para el análisis de la política educativa supranacional, propuesto por el comparatista español Javier M. Valle, en complemento con la teoría de los sistemas sociales autorreferenciales, desarrollada por el sociólogo alemán Niklas Luhmann. Con tal interés académico, el artículo se ha estructurado en cuatro apartados: 1) introducción a la temática (autonomía escolar), 2) implicaciones de la globalización para la educación comparada, 3) análisis para la construcción de un estado de la cuestión, y 4) conclusión a manera de cierre, donde se argumenta que los efectos que producen los modelos de autonomía en las escuelas públicas de educación básica, son inciertos; causa y efecto quedan relativizados, se transforman el uno en el otro, es decir, se crea lo improbableIn this article we present an overview of the main epistemic approaches in research on educational policy in the world, focusing specifically on the contributions and limitations of the production of knowledge of management autonomy school and its relationship to the Globally Structured Educational Agenda (GSEA), with the ultimate intention of describing the positioning of public policy in its supranational, national and sub-national dimension, for which the methodological approach for the analysis of supranational education policy is adopted, proposed by comparatist spanish Javier M. Valle, in complement with the theory of self-referential social systems, developed by the german sociologist Niklas Luhmann. With such academic interest, the development of this communication is structured into four sections, namely: introduction to the issue of school autonomy: 1) implications of globalization for comparative education, 2) analysis axes, 3) construction of a state of affairs, and 4) conclusion in closing, where it is argued that the effects of models of autonomy in public elementary schools, are uncertain. Cause and effect are relativized, are transformed into each othe

Identificação de peptideos ligantes a superfície de epimastigotas de Trypanosoma cruzi

Orientador: Prof. Dr. Wanderson Duarte da RochaCoorientadora: Profa. Dra. Juliana Ferreira de MouraDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Ciências (Bioquímica). Defesa : Curitiba, 28/02/2020Inclui referências: p. 70-86Resumo: A doença de Chagas, também conhecida como tripanossomíase americana, é uma doença potencialmente fatal causada pelo parasito protozoário Trypanosoma cruzi, que é transmitida por insetos da família Reduviidae. Uma vez que o tratamento convencional com drogas nitro-heterocíclicas mostra reações adversas graves e eficiência questionável, diferentes grupos testaram abordagens baseadas em polipeptídeos para interferir com o ciclo celular parasito em outros Tripanosomatídeos. Por exemplo, os nanobodies contra VSG de T. brucei estão sendo expressos em bactérias simbiontes com o objetivo de bloquear a transmissão do parasito, ou usado para melhorar a entrega do fármaco, combinando-os com nanopartículas ou peptídeos líticos. Essas estratégias são apoiadas pelo fato de que os componentes de superfície são candidatos para desenvolver ligantes de superfície para prejudicar a função, pois podem atuar como fatores de virulência. Neste trabalho, usamos uma abordagem de phage display para identificar derivados de peptídeos de duas bibliotecas de peptídeos, LX15 (15 aa) e LX8CX8 (17 aa) (onde X corresponde a qualquer aminoácido). Depois de testar diferentes condições de biopanning usando epimastigotas vivos ou fixados, nós sequenciamos 10 clones que codificam o mesmo polipeptídeo, aqui chamado EPI18. O bacteriófago que codifica EPI18 liga-se a epimastigotes de cepas distintas. Para confirmar estes resultados, este polipeptídeo foi sintetizado e biotinilado para realizar ELISA, citometria de fluxo e análises de microscopia confocal. Nossos ensaios mostram a especificidade e capacidade de ligação para a superfície de epimastigotes em comparação com o peptídeo não relacionado. Também isolamos bacteriófagos de uma biblioteca de peptídeos de bacteriófagos estruturalmente semelhantes (LX15), através do sequenciamento de 30 clones, identificamos 13 sequências diferentes e 4 motivos conservados, sendo que um desses motivos identificados comparte similaridade com o péptido EPI18. Vários peptídeos identificados (EPI18 e de LX15) apresentaram semelhanças com proteínas lipocalinas, que podem ter relevância na biologia da interação, contudo isto deve ser testado. Esses resultados sugerem que os peptídeos identificados aqui possam ter potenciais aplicações biotecnológicas, como estratégias baseadas em peptídeos para controlar a transmissão do parasito.Abstract: Chagas disease, also known as American trypanosomiasis, is a potentially lifethreatening illness caused by the protozoan parasite Trypanosoma cruzi, which is transmitted by insects from Reduviidae family. Since the conventional treatment with nitroheterocyclic drugs shows serious adverse reactions and questionable efficiency, different group have tested polypeptide-based approaches to interfere with parasite cell cycle in other Trypanosomatids. For example, nanobodies against T. brucei VSGs are being expressed in endosymbiont bacteria aiming to block parasite transmission or used to improve drug delivery by combining them to nanoparticles or lytic peptides. These strategies are supported by the fact that surface players are candidates to develop surface ligand to impair their function since they may act as virulence factors. In this work, we used a phage display approach to identify peptides derivate of two peptide libraries, LX15 (15 aa) and LX8CX8 (17 aa) (where X corresponds to any amino acid). After testing different biopanning conditions using live or fixed epimastigotes, we sequenced 10 clones encoding the same polypeptide, named here as EPI18. The bacteriophage encoding EPI18 binds to epimastigotes from distinct strains. To confirm these results this polypeptide was synthetized and biotinylated to perform flow cytometry and confocal microscopy analyses. Our preliminary assays show its specificity and binding capacity towards to epimastigotes surface compared to unrelated peptide. We also isolated bacteriophages from a similar phage display peptide library (LX15), through sequencing of 30 clones, we identified, 13 different sequences and 4 conserved motifs, one of these identified motifs shares similarity with of EPI18 peptide. Lipocalins proteins were identified in bioinformatics analysis as corresponding sequences of 6 of our identified peptides, however its relevance needs to be addressed. These results suggest that the peptides identified here may have potential biotechnological applications such as peptide-based strategies to control parasite transmission

SEOM–GEICAM–SOLTI clinical guidelines in advanced breast cancer (2022)

Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer

Papel de los radicales libres en el envejecimiento de las membranas celulares

Desde que Harman (1956) propusiera el estrés oxidativo, derivado de la utilización del oxígeno en el metabolismo de los organismos vivos, como una de las principales causas del envejecimiento fisiológico, la investigación se ha focalizado en el estudio de sus efectos sobre las diferentes estructuras celulares. En el presente trabajo revisamos el efecto de las especies reactivas del oxígeno sobre los lípidos, principal componente estructural de las membranas biológicas, a través del mecanismo de peroxidación lipídica. Las numerosas investigaciones realizadas en este ámbito aportan una fuerte evidencia a favor de que las especies químicas derivadas del oxígeno están implicadas en la pérdida de fluidez de las membranas y la consiguiente pérdida de funcionalidad celular, constituyendo un importante factor en el proceso de envejecimiento.<br /

Oxygen-sensing by ion channels and mitochondrial function in carotid body glomus cells

Carotid body glomus cells release transmitters in response to hypoxia due to the increase of excitability resulting from inhibition of O2-regulated K+ channels. The mechanisms involved in the detection of changes of O2 tension are unknown. Inhibition of the mitochondrial electron transport chain (ETC) at proximal and distal complexes induces external Ca2+-dependent catecholamine secretion. At saturating concentration of the ETC inhibitors, the cellular response to hypoxia is maintained. However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dosedependent manner. The effect of rotenone is not mimicked by complex I inhibitors acting on different sites. We have also generated a knock-out mouse lacking SDHD, the small membrane-anchoring protein of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. Homozygous Sdhd -/- animals die at early embryonic stages. Heterozygous Sdhd +/- mice show a general, non-compensated, deficiency of complex II activity, and abnormal enhancement of resting carotid body secretion rate due to decrease of K+ conductance and persistent Ca2+ influx into glomus cells. However, responsiveness to hypoxia of carotid bodies from Sdhd +/- mice remains intact. These data strongly suggest that sensitivity to hypoxia of carotid body glomus cells is not linked in a simple way to mitochondrial electron flow. Nevertheless, it is possible that a rotenone-sensitive molecule critically participates in acute carotid body oxygen sensing

Magneto-optical kerr effect in resonant subwavelength nanowire gratings

Periodic arrays of nanorods can present a resonant response at specific geometric conditions. We use a multiple scattering approach to analyze the optical response of subwavelength nanowire gratings made of arbitrary anisotropic materials. When the rods are made of magneto-optical dielectrics we show that there is a complex interplay between the geometric resonances of the grating and the magneto-optical Kerr effects (MOKE) response. As we will show, for a given polarization of the incident light, a resonant magneto-optical response can be obtained by tuning the incidence angle and grating parameters to operate near the resonance condition for the opposite polarization. Our results could be important to understand and optimize MOKE structures and devices based on resonant subwavelength gratings and could open new perspectives in sensing applicationsThis work was supported by Ikerbasque Visiting Fellowship (JJS), EU Project Nanomagma NMP3- SL-2008-214107, by LABEX WIFI (Laboratory of Excellence within the French Program ‘Investments for the Future’) under references ANR-10-LABX-24 and ANR-10-IDEX-0001- 02 PSL*, by the Spanish Ministerio de Ciencia e Innovación through CSD2007-00046 (NanoLight.es); CSD2008-00023 (Funcoat); FIS2009-13430 ; MAT2011-29194-C02-01; FIS2012-3611 and by the Comunidad de Madrid P2009/TIC-147

Dynamical and temporal characterization of the total ozone column over Spain

As the ozone is one of the most relevant variables in the climate system, to get further in its long-term characterization is a critical issue. In this study, measurements of total ozone column (TOC) from five well-calibrated Brewer spectrophotometers placed in the Iberian Peninsula are analyzed. The temporal trend rate for TOC is +9.3 DU per decade for the period 1993–2012 in Central Iberian Peninsula. However, the low TOC levels during 2011 and 2012 over the study region notably reduce this rate. Empirical linear relationships are established between TOC and pressure, height, and temperature of the tropopause. The linear fits showed seasonal and latitudinal dependence, with stronger relationships during winter and spring. Events with the presence of a double tropopause (DT) are proved to be characteristic of the study region. The decrease in TOC levels when these anomalous events occur is quantified around 10 % in winter and spring with respect to the usual cases with a single tropopause. The total weight of the DT events with respect to the annual values is about 20 %, with a negligible occurrence in summer and autumn and being latitudinal-dependent. The North Atlantic Oscillation (NAO) index explains 30 % of the total ozone variability in winter. The DT events are found to be more frequent during phases with positive NAO.This work was partially supported the Ministerio de Ciencia e Innovación through project CGL2011-29921-C02-01

Referees', coaches', and experts' opinions on the utilisation of the rules in the teaching-learning process of mini-basketball

Rules affect the technical-tactical elements since they establish the limits on the players' actions in relation to the ball and the rest of the players. However, there are very few references that discuss this topic. Thus, it was decided to get familiar with the opinions of experts, referees, and coaches regarding the utilisation of the rules and regulations at the mini-basketball stage. The sample was made up of 9 subjects who were interviewed: three coaches, three referees, and three experts. All had university degrees and certification from the federation as well as experience in the minibasketball division. The instrument that was used was the semi-structured interview. The Delphi method was followed for the design of the interview, and 5 university professors participated in selecting the dimensions and questions. After the definitive composition and the pilot study, the various professionals from the sample were contacted and interviewed. The content of the interviews was recorded and transcribed. The coding was done by four researchers, and the reliability was assured by the Kappa index, of which the mean index was K = .78. The analysis was done with MXQDA 10 and SPSS 20. The participants insist on the importance of teaching the rules to the players when they begin playing basketball, given that this learning allows them to understand the internal logic of the game. Further, they explain the need for this relationship in the learning process and it even opens up the possibility for programming around the rules, given that they are what give the game and its technical-tactical elements meaning