305 research outputs found
Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells
Supplemental information can be found online at https://doi.org/10.1016/j.molcel.2022.10.005ACKNOWLEDGMENTS P.A.-M was supported by a Marie Sklodowska-Curie Actions individual fellowship and the Beug Foundation. A.V. was supported by Fonds Wetenschappelijk Onderzoek (FWO Vlaanderen). J.E.-H. was supported by an MRC studentship. J.C.A was supported by a Cancer Research UK Career Development Fellowship (C47559/A16243). S.-M.F. acknowledges funding from the European Research Council under the ERC Consolidator grant agreement no. 771486–MetaRegulation, FWO Projects, Fonds Baillet Latour, KU Leuven- FTBO/Internal Funding, Stichting Tegen Kanker and the King Baudouin Foundation. Work in the A.J.F. group was supported by a Wellcome Trust-ISSF grant, funding from Barts Charity (MGU0404), and by a Cancer Research UK Centre Grant to Barts Cancer Institute (C355/A25137). The illustrations in the graphical abstract and Figure 5F were created using BioRender.com.Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis—the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.Marie Sklodowska-Curie ActionsBeug FoundationFonds Wetenschappelijk Onderzoek (FWO Vlaanderen)Cancer Research UK Career Development Fellowship (C47559/A16243)European Research Council under the ERC Consolidator grant agreement no. 771486–MetaRegulationFWO ProjectsFonds Baillet LatourKU Leuven- FTBO/Internal FundingWellcome Trust-ISSF grantBarts Charity (MGU0404)Cancer Research UK Centre Grant to Barts Cancer Institute (C355/A25137
Development of Cellular Models to Study Efficiency and Safety of Gene Edition by Homologous Directed Recombination Using the CRISPR/Cas9 System
In spite of the enormous potential of CRISPR/Cas in basic and applied science, the levels of
undesired genomic modifications cells still remain mostly unknown and controversial. Nowadays,
the efficiency and specificity of the cuts generated by CRISPR/Cas is the main concern. However,
there are also other potential drawbacks when DNA donors are used for gene repair or gene knock-ins.
These GE strategies should take into account not only the specificity of the nucleases, but also
the fidelity of the DNA donor to carry out their function. The current methods to quantify the
fidelity of DNA donor are costly and lack sensitivity to detect illegitimate DNA donor integrations.
In this work, we have engineered two reporter cell lines (K562_SEWAS84 and K562GWP) that
efficiently quantify both the on-target and the illegitimate DNA donor integrations in a WAS-locus
targeting setting. K562_SEWAS84 cells allow the detection of both HDR-and HITI-based donor
integration, while K562GWP cells only report HDR-based GE. To the best of our knowledge, these are
the first reporter systems that allow the use of gRNAs targeting a relevant locus to measure efficacy
and specificity of DNA donor-based GE strategies. By using these models, we have found that the
specificity of HDR is independent of the delivery method and that the insertion of the target sequence
into the DNA donor enhances efficiency but do not affect specificity. Finally, we have also shown that
the higher the number of the target sites is, the higher the specificity and efficacy of GE will be.Spanish ISCIII Health Research FundEuropean Union (EU)
PI15/02015
PI18/00337
PI18/00330CECEyU of the Junta de Andalucia FEDER/European Cohesion Fund (FSE)
2016000073391-TRA
2016000073332-TRA
PI-57069
CARTPI-0001-201
PAIDI-Bio326
PI-0014-2016CSyF of the Junta de Andalucia FEDER/European Cohesion Fund (FSE)
2016000073391-TRA
2016000073332-TRA
PI-57069
CARTPI-0001-201
PAIDI-Bio326
PI-0014-2016Nicolas Monardes regional Ministry of Health contract
0006/2018Fundacion Poco FrecuenteSpanish Government
FPU17/04327
FPU17/02268ISCIII through a PFIS fellowship
FI19/00163SMSI
PEJ-2018-001760-
Influencia de un Programa de Expresión Corporal en el Autoconcepto Físico en un grupo de escolares
El objetivo de este estudio, se ha basado en la percepción y posible mejora del Autoconcepto físico de los adolescentes, mediante la promoción de actividades rítmico expresivas en la E.S.O. Concretamente se ha llevado a cabo con los alumnos de 4º de Educación Secundaria del Colegio Santa Ana de Huesca. El diseño es un pre- post con grupo control. El cuestionario recoge información acerca del autoconcepto físico y sus percepciones, mediante el Cuestionario de Autoconcepto Físico (CAF- Goñi et al, 2006), dado que este término en la adolescencia es un aspecto crítico en estas edades, pensamos que era un punto fuerte el poder trabajarlo y observar cómo por medio de distintas actividades rítmico expresivas y dadas las particularidades de este tipo de motricidad, podía cambiar la percepción del mismo en los jóvenes. Los datos obtenidos del instrumento mencionado se han tratado con los programas EXCEL y SPSS. El programa de intervención, ha consistido en la puesta en marcha de una Unidad Didáctica de Expresión Corporal, compuesta por sesiones de diferentes actividades rítmicas, con objetivo común centrado en observar y analizar el cambio de la percepción del autoconcepto físico desde un plano lúdico-recreativo. Finalizado el trabajo, se reflejan las valoraciones obtenidas, pudiendo transferir los resultados a otros proyectos
Política Urbana en el Estado de México 2005-2011: Análisis del programa Ciudades del Bicentenario
Uno de los programas nodales de la política urbana en el Estado de México durante el periodo de gobierno 2005-2011 fue el denominado “Ciudades del Bicentenario”; mismo que tuvo como propósito central orientar el crecimiento urbano hacia seis municipios considerados estratégicos por sus condiciones naturales, existencia de reservas de suelo, así como mayor capacidad para absorber nuevos núcleos poblacionales y, de esa manera, evitar la dispersión de los asentamientos humanos tal y como había ocurrido en decenios pasados. Mediante la implementación de una política urbana de impulso, que se adicionó a las políticas de control y consolidación que hasta 2005 se reconocían como únicas viables, se llevó a cabo un importante número de autorizaciones de nuevos desarrollos habitacionales, bajo la denominación técnica de Conjuntos Urbanos, en los municipios de Almoloya de Juárez, Atlacomulco, Jilotepec, Huehuetoca, Zumpango y Tecámac. Si bien se estableció un propósito general para el programa Ciudades del Bicentenario, en este estudio se demuestra que no existió una instrumentación equilibrada de las estrategias establecidas en él y que los efectos en términos de incrementos poblacionales y en el número y características de las viviendas autorizadas han sido desiguales entre los municipios seleccionados, generando efectos contrarios a los enunciados en dicho programa
APLICACIÓN DE LA EVALUACION FORMATIVA, MEDIANTE EL MODELO DE APRENDIZAJE COOPERATIVO EN UNA UNIDAD DIDACTICA DE PARKOUR
Se trata de un etudio cuasi - experimental pre - pot, en el que se muetra la percepcion de cuatro clases sobre un sistema de evaluacion formativa y sobre la aplicacion del modelo de aprendizaje cooperativo, implementado en una unidad didactica de parkour. En dicho estudio, el alumnado mostrara su percepcion a cerca de este tipo de sitema de evaluacion, tambien valoraran mediante un instrumento validado la correcta o incorrecta aplicacion del modelo pedagogico y se realizara una comparativa entre dos grupos de dicha muetra.<br /
Determinantes de la información sostenible divulgada por las empresas de electricidad: un estudio internacional / Determining factors of sustainable information disseminated by electric power companies: an international study
Resumen
El objetivo del artículo es examinar los factores que afectan a la información voluntaria suministrada por las organizaciones del sector eléctrico en sus memorias de sostenibilidad. La metodología utilizada consiste en aplicar un modelo de regresión Tobit, para medir la influencia de las variables independientes sobre un indicador de sostenibilidad. La muestra objeto de estudio la constituyen 40 corporaciones eléctricas, fundamentalmente europeas y americanas, incluidas en el listado de la Global Reporting Initiative.
Los resultados sugieren que; la rentabilidad, la participación en el mercado y la evaluación de la información emitida, influyen en la información que figura en las memorias de sostenibilidad.The aim of this article is to examine factors affecting to the voluntary information that electricity sector organizations provide in their sustainability reports. The methodology involves the application of Tobit regression model to measure the influence of independent variables on an indicator of sustainability. The study sample consists of 40 electrical corporations, mainly European and American, including in the list of the Global Reporting Initiative.
The results revealed that the market share, return on investment and the evaluation of the information are variables that influence, significantly, on the information contained in sustainability reports
Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi
This publication is based upon work from COST Action Gene Editing
for the treatment of Human Diseases, CA21113 (https://www.
genehumdi.eu) supported by COST (European Cooperation of Science and Technology). The study was also supported by the Consejería de Universidad, Investigación e Innovación under Plan Andaluz
de Investigación, Desarrollo e Innovación (PAIDI 2020) (ProyExcel_00875) de la Junta de Andalucía, and by Consejería de Salud y familia de la Junta de Andalucía/FEDER (PECART-0027-2020), K.B. held
Nicolas Monardes contract from Consejería de Salud y Consumo
de la Junta de Andalucía.The European Cooperation in Science and Technology (COST)
is an intergovernmental organization dedicated to funding and
coordinating scientific and technological research in Europe,
fostering collaboration among researchers and institutions
across countries. Recently, COST Action funded the "Genome
Editing to treat Human Diseases" (GenE-HumDi) network,
uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech
firms, and patient advocacy groups. GenE-HumDi’s primary
objective is to expedite the application of genome editing for
therapeutic purposes in treating human diseases. To achieve
this goal, GenE-HumDi is organized in several working groups,
each focusing on specific aspects. These groups aim to enhance
genome editing technologies, assess delivery systems, address
safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard
procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore,
GenE-HumDi aims to communicate its findings to the public
in accessible yet rigorous language, emphasizing genome editing’s potential to revolutionize the treatment of many human
diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts
in the field, discussing recent breakthroughs in delivery
methods, safety measures, clinical translation, and regulatory
aspects related to gene editing.COST (European Cooperation of Science and Technology)Consejería de Universidad, Investigación e Innovación, Junta de Andalucía PAIDI 2020, ProyExcel_00875Junta de Andalucia/FEDER (PECART-0027-2020)Consejería de Salud y Consumo
de la Junta de Andalucí
Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release
Despite the large number of polymeric nanodelivery systems that have been recently
developed, there is still room for improvement in terms of therapeutic efficiency. Most reported
nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug
leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present
a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular,
we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled
pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520)
cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory
concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which
leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of
this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining.
In summary, we successfully characterized and validated a pH responsive therapeutic polymeric
nanodevice in vitro for controlled anticancer drug release.Spanish Ministry of Economy and Competitiveness (MINECO)
BIO2016-80519Health Institute Carlos III (ISCIII)
DTS18/00121Andalusian Regional Government
PAIDI-TC-PVT-PSETC-2.
La Guerra Civil española en el cine actual: Encontrarás Dragones
La historia del cine español recoge numerosos films sobre la Guerra Civil española. El presente artículo pretende realizar un recorrido por esta filmografía para, finalmente, analizar el último film sobre esta temática, estrenado en 2011: There Be Dragons (Encontrarás dragones), de Roland Joffé. Se analizarán una serie de características propias de este largometraje como la fusión de géneros y la oposición ideológica como eje central y, finalmente se detallará el márketing llevado a cabo en la red y su presencia en las redes sociales, hoy en auge como medio publicitario.The history of Spanish cinema includes many films about the Civil War. This article aims to take a tour of the films to finally discuss the latest film on this subject, released in 2011: There Be Dragons, Roland Joffé. Identified a number of characteristics of this film: the fusion of genres and ideological opposition as the core and, finally, will detail the marketing carried out on the web and social networking presence, on the rise as an advertising mediu
The complex world of interactivity: emotions and social networks
El objetivo de la presente investigación es discernir cómo debe plantearse un aprendizaje en nuevas tecnologías, en especial, en redes sociales. Para esto, se analizará la dinámica
neurológica y psicológica de las emociones y cómo se desenvuelven en el ámbito de las redes sociales. La metodología que emplearemos será acudir a diversos estudios neurológicos y psicológicos actuales, en especial de Antonio Damasio, para analizar posteriormente qué sucede con las emociones cuando nos comunicamos a través de redes sociales, tomando como referente un experimento neurológico de dicho autor en el cerebro de varios voluntarios que muestra la
aparición de diversos tipos de emociones. Por último, extrapolaremos este experimento a la
aparición de emociones si se utiliza como medio de comunicación las redes sociales y
realizaremos algunas conclusiones acerca de la dirección a la que debe tender el aprendizaje de nuevas tecnologías, en especial, redes sociales, teniendo en cuenta dichas observaciones.The objective of this research is to discern how it should consider learning on new technologies, especially in social networks. For this, we examine the neurological and psychological dynamics of emotions and how they develop in the field of social networks. Our methodology will go to various neurological and psychological studies today, including Antonio Damasio and how to analyze what appens when we communicate emotions through social networks, by reference to a neurological experiment that copyright in the brain several volunteers that shows the appearance of various types of emotions. Finally, we extrapolate this experiment to the appearance of emotions when social networks are used as media and will make some conclusions about the direction you should
aim to learn new technologies, especially social networks, taking into account such observations
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