966 research outputs found

    TBL1 is required for the mesenchymal phenotype of transformed breast cancer cells

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    The epithelial-to-mesenchymal transition (EMT) and its reversion (MET) are related to tumor cell dissemination and migration, tumor circulating cell generation, cancer stem cells, chemoresistance, and metastasis formation. To identify chromatin and epigenetic factors possibly involved in the process of EMT, we compare the levels of expression of epigenetic genes in a transformed human breast epithelial cell line (HMEC-RAS) versus a stable clone of the same cell line expressing the EMT master regulator ZEB1 (HMEC-RAS-ZEB1). One of the factors strongly induced in the HMEC-RAS-ZEB1 cells was Transducin beta-like 1 (TBL1), a component of the NCoR complex, which has both corepressor and coactivator activities. We show that TBL1 interacts with ZEB1 and that both factors cooperate to repress the promoter of the epithelial gene E-cadherin (CDH1) and to autoactivate the ZEB1 promoter. Consistent with its central role, TBL1 is required for mesenchymal phenotypes of transformed breast epithelial and breast cancer cell lines of the claudin-low subtype. Importantly, a high expression of the TBL1 gene correlates with poor prognosis and increased proportion of metastasis in breast cancer patients, indicating that the level of TBL1 expression can be used as a prognostic marker.Ministerio de Economía y Competitividad BFU2014-53543-P, BFU2017-85420-RJunta de Andalucía BIO-32

    Insight into the dynamics of low temperature dielectric relaxation of ordinary perovskite ferroelectrics

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    The temperature dependence of the dielectric response of ordinary ferroelectric materials exhibits a frequency-independent anomalous peak as a manifestation of the ferroelectric to paraelectric phase transition. A second anomaly in the permittivity has been reported in different ferroelectric perovskite-type systems at low temperatures, often at cryogenic temperatures. This anomaly manifests as a frequency-dependent local maximum, which exhibits similar characteristics to that observed in relaxor ferroelectrics around their phase transition. The origin of this unexpected behavior is still controversial. In order to clarify this phenomenon, a model-free route solution is developed in this work. Our findings reveal the same critical linear pattern/glass-like freezing behavior previously observed for glass-forming systems. Contrary to current thought, our results suggest that a critical-like dynamic parameterization could provide a more appropriate solution than the conventional Vogel–Fulcher–Tammann equation. The implemented methodology may open a new pathway for analyzing relaxation phenomena in other functional materials like relaxor ferroics.Postprint (published version

    The generalized Vogel-Fulcher-Tamman equation for describing the dynamics of relaxor ferroelectrics

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    Relaxor ferroelectrics (RF) are outstanding materials owing to their extraordinary dielectric, electromechanical, and electro-optical properties. Although their massive applications, they remain to be one of the most puzzling solid-state materials because understanding their structural local order and relaxation dynamics is being a long-term challenge in materials science. The so-called Vogel-Fulcher-Tamman (VFT) relation has been extensively used to parameterize the relaxation dynamics in RF, although no microscopic description has been firmly established for such empirical relation. Here, we show that VFT equation is not always a proper approach for describing the dielectric relaxation in RF. Based on the Adam-Gibbs model and the Grüneisen temperature index, a more general equation to disentangle the relaxation kinetic is proposed. This approach allows to a new formulation for the configurational entropy leading to a local structural heterogeneity related order parameter for RF. A new pathway to disentangle relaxation phenomena in other relaxor ferroics could have opened.Postprint (published version

    Unfolding kinetic fragility in relaxor ferroelectrics

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    The fragility parameter is one of the most important material constants that is extensively used in glass science, playing a central role in the enhancement of the understanding the glass formation process of disordered systems. Although fragility has been widely used, this concept has never been precisely defined and evaluated in relaxor ferroelectrics. Here, we have filled up this scientific gap. Based on a generalized Vogel-Fulcher-Tammann equation, the fragility parameter is introduced for relaxor ferroelectrics. The new formulation has been quantitatively assessed by combining dielectric spectroscopy and pyroelectric measurements on canonical relaxors. A clear correlation between the fragility and a new local structural heterogeneity related order parameter elucidates new information about the ferroelectric order of relaxor ferroelectrics. A new pathway to disentangle relaxation phenomena in other relaxor ferroics could have opened.Peer ReviewedPostprint (author's final draft

    Evidence for a dynamics crossover and its implication on the freezing temperature determination of relaxor ferroelectrics

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    Relaxor ferroelectrics are characterized by a broadened and dispersive permittivity peak in their temperature-dependent dielectric spectra. Although several models have been proposed to explain the nature of these materials, understanding their relaxation dynamics still remains open and requires additional theoretical and experimental explanations. Particularly, a precise determination of the freezing temperature still remains controversial because the influence of dynamic ruptures at temperatures approaching the freezing states (dynamic crossovers) has never evaluated before. In this paper, a model-free approach for describing the super-Arrhenius behaviour in glassy systems is validated for relaxor ferroelectrics. As a result, a predicted dynamic change at a specific temperature (crossover temperature) is evidenced by a derivative-based representation of the relaxation time data. The Stickel function is suggested as a more straightforward but model-dependent method for obtaining the dynamic crossover temperature. Furthermore, the divergence (freezing) temperature is obtained on the basis of the Grüneisen-style activation energy temperature index without assuming any model equation for parameterizing the relaxation data. The influence of the dynamic change occurrences on the freezing temperature determination is also considered, showing that the dynamic crossover temperature determination is a key factor for a proper finding of the freezing temperature in relaxor ferroelectrics.Postprint (author's final draft

    Facteurs affectant la concentration de cellules somatiques dans le lait des chèvres de la race Mur -ciano-granadina: Résultats préliminaires

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    Somatic cell count (SCC) in milk is an indicator of the udder´s health. The National Association of Murciano-granadina Goat Breeders (CAPRIGRAN) has developed a program in order to improve the quantity and the quality of milk, being the SCC an important milk quality aspect. The aim of this study is to identify the factors significantly affecting the SCC content in milk of Murcia-granadina goats. Data from 18 farms were collected, with a total of 5799 lactations. 10 variables have been analyzed, 7 quantitative (number of births, lactation period days, drying period days, milk production per day, fat contain, protein contain and SCC) and 3 qualitative (type of system, drying treatment and milking valorization). The most influencing quantitative variables in the SCC are: milk production per day and lactation period days and the drying period days. The most influencing qualitative variables are: type of system and milking valorization. Further studies are necessary for better understanding the influence of type of system on the SCC, especially on factors related to facilities and the feeding.La concentration de cellules somatiques (CCS) dans le lait est un indicateur de la santé des ma - melles. L’Association d’Éleveurs de chèvres de la Race Murciano-granadina (CAPRIGRAN) a mis au point un programme pour améliorer la quantité et qualité du lait, étant la CCS un important aspect lié à la qualité. L’objet de ce travail est d’identifier les différents facteurs affectant le contenu en cellules somatiques du lait des chèvres de la race Murciano-granadina. On a utilisé les données de 18 fermes, avec un total de 5799 lactations et on a analysé 10 variables, 7 quantitatives (numéro de naissances, jours du période de lactation, jours du période de séchage, production par jour, contenu en graisse, contenu en protéine et CCS) et 3 qualitatives (type de système, traitement de séchage et valorisation de la traite). Les variables quantitatives plus influentes sur la CCS sont la production de lait par jour, la durée du période de lactation et la durée du période de séchage. Les variables quantitatives plus influentes sur la CCS sont le type de système de production et la valorisation du procès de traite. Plus d’études pour mieux comprendre l’influence du type de système de production sur le CCS seraient nécessaires, spécialement au sujet des aménagements et de l’alimentation des chèvres

    Análisis de regularidad en fibrilación ventricular: aplicación a registros de mapeado cardíaco

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    Las técnicas utilizadas en el análisis de la señal de fibrilación ventricular (FV), obtenida mediante sistemas de mapeado utilizando matrices de electrodos, extraen información del proceso a partir de parámetros calculados principalmente en el dominio del tiempo o de la frecuencia. El presente trabajo plantea la aplicación del índice de regularidad (IR), propuesto inicialmente para caracterizar la fibrilación auricular humana, a la señal de FV en un modelo experimental de corazón animal. Los resultados obtenidos muestran que el IR permite extraer información de los mapas de FV no disponible de forma directa cuando se estudian mediante los métodos clásicos en el tiempo o la frecuencia, cuantificando el grado de modificación en la morfología de las ondas de activación durante la FV

    Relación entre el espectro y la regularidad en la señal de fibrilación ventricular modificada por el ejercicio físico

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    El presente trabajo estudia las modificaciones intrínsecas que el ejercicio físico produce en la respuesta cardíaca durante la FV. Se han calculado dos parámetros relacionados con el espectro de la señal (FD: frecuencia dominante, y EN: energía normalizada), y otro relacionado con la regularidad de las OAL (IR: índice de regularidad), Se ha realizado un análisis de correlación entre los tres parámetros para valorar su grado de complementariedad. Se consideraron dos grupos de conejos: control (G1: sin entrenamiento, N=10) y entrenados (G2, N=9). Se utilizó un electrodo matricial de 240 canales localizado en ventrículo izquierdo de corazón aislado de conejo perfundido mediante un sistema de Langendorff. La FV se indujo por estimulación a frecuencias crecientes. Los resultados muestran que el grupo entrenado presenta una mayor regularidad de la señal (IR: G1: 0,757+-0,091; G2: 0,845+-0,084; p<0.001), así como menor FD (G1: 18.23±2.96Hz; G2: 14.13+-1.73Hz; p<0.001) y dispersión espectral (EN: G1: 0,138+-0.105; G2: 0,293+-0,176; p<0.001). El análisis de las relaciones entre parámetros muestra correlaciones significativas entre los parámetros para todos los casos excepto para IR y FD en G2, por lo que estos parámetros proporcionan información complementaria, ya que analizan aspectos diferentes de la señal como la morfología de las ondas de activación y su frecuencia. La existencia de correlación entre ambas para G1 puede ser debida a otras causas, tales como las modificaciones en ambos factores inducidas por la presencia de reentradas o colisiones entre frentes de activación.. Como conclusión, los resultados obtenidos sugieren que el entrenamiento físico produce una respuesta cardíaca más estable ante FV, debida a modificaciones intrínsecas en las características electrofisiológicas cardíacas
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