Statefinder diagnostic and stability of modified gravity consistent with holographic and new agegraphic dark energy

Recently one of us derived the action of modified gravity consistent with the holographic and new-agegraphic dark energy. In this paper, we investigate the stability of the Lagrangians of the modified gravity as discussed in [M. R. Setare, Int. J. Mod. Phys. D 17 (2008) 2219; M. R. Setare, Astrophys. Space Sci. 326 (2010) 27]. We also calculate the statefinder parameters which classify our dark energy model.Comment: 12 pages, 2 figures, accepted by Gen. Relativ. Gravi

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Changes in adipose tissue plasticity after bariatric surgery and their role in the improvement of obesity-associated comorbidities

Adipose tissue (AT) is considered a plastic and dynamic endocrine organ with obesity driving changes in its biomechanical properties as well as in its extracellular matrix (ECM) remodelling, inflammation and mechanotransduction profiles, leading to the impairment of whole-body homeostasis. To achieve important and sustained weight loss as well as for the resolution of obesity-associated diseases, bariatric surgery (BS) is considered the most effective option in adequately selected patients. Despite great efforts to understand the processes involved in both, the development of dysfunctional AT and the favourable outcomes of BS, the underlying biological mechanisms have not been fully disentangled. Therefore, the objective of the present PhD thesis is to evaluate changes in AT plasticity together with their associations with the inflammation profile as well as ECM remodelling and mechanotransduction properties in an animal model of diet-induced obesity (DIO) and in patients with obesity. At the same time, we aimed to analyse the effect of BS on these biological processes, beyond the mere weight loss. We found that changes in the biomechanical properties of AT in obesity, including decreased Young’ modulus (E), ultimate tensile strength (UTS) and strain at UTS, were associated with the deterioration of body homeostasis. In this line, obesity induced changes in the inflammation, fibrosis and ECM remodelling profiles not only in AT but also in the liver being also related to the development of obesity comorbidities. Our findings also provide new insights into AT adaptation after BS beyond caloric restriction, being demonstrated by significant changes in the mechanotransduction and inflammatory profiles together with the decrease in the crosslinking and synthesis of collagens as well as an increase in its degradation. Our data also supports the notion that the higher blood vessel density found in AT after BS is involved in the increased E, UTS and strain at UTS values, providing at the same time higher stiffness and increased strain capacity. Furthermore, the inhibition of NLRP3, a key component of the inflammasome involved in the regulation of inflammation, in visceral adipocytes significantly blocked inflammation and fibrosis suggesting its potential to regulate the development of obesity-associated comorbidities. In terms of fibrosis-inducing factors, we also showed a novel role of dermatopontin in the pathological AT ECM remodelling during obesity. Finally, we proposed that the measurement of the Adiponectin/Leptin ratio after BS might constitute a significant factor for evaluating the remission of type 2 diabetes after bariatric procedures.El tejido adiposo (TA) es un órgano endocrino plástico y dinámico, que experimenta cambios en sus propiedades biomecánicas, así como en los perfiles de remodelación de su matriz extracelular (MEC), inflamación y mecanotransducción con la obesidad. La cirugía bariátrica (CB) constituye la opción más efectiva para lograr una pérdida de peso importante y sostenida en el tiempo, así como para la resolución de comorbilidades asociadas a la obesidad en pacientes adecuadamente seleccionados. A pesar de los grandes esfuerzos realizados para comprender los procesos involucrados tanto en el desarrollo del TA disfuncional como en los efectos favorables de la CB, no se han desentrañado completamente los mecanismos biológicos subyacentes. Por todo ello, el objetivo de la presente tesis doctoral es evaluar los cambios en la plasticidad del TA, además de estudiar su relación con el perfil inflamatorio, así como con el remodelado de la MEC y propiedades de mecanotransducción en un modelo animal de obesidad inducida por dieta (OID) y en pacientes con obesidad. Al mismo tiempo nos propusimos analizar el efecto de la CB sobre dichos procesos biológicos, más allá de la mera pérdida de peso. Nuestros resultados muestran que los cambios en las propiedades biomecánicas del TA en animales con obesidad, incluyendo la disminución del módulo de Young (E), la resistencia máxima a la tracción (RMT) y la tensión en RMT, se asociaron con el deterioro de la homeostasis corporal. En esta línea, la obesidad indujo cambios en los perfiles de inflamación, fibrosis y remodelado de la MEC no exclusivamente en el TA, sino también en el hígado, relacionándose también con el desarrollo de comorbilidades asociadas a la obesidad. Los datos obtenidos revelan nuevos hallazgos sobre la adaptación del TA tras CB más allá de la restricción calórica, demostrando cambios significativos en los perfiles inflamatorios y de mecanotransducción junto con la disminución en la conformación reticulada de colágenos y su síntesis, así como un aumento en su degradación. Nuestros resultados también respaldan la noción de que la mayor densidad de vasos sanguíneos encontrada en el TA tras CB está asociada con un aumento de E, RMT y tensión en RMT, proporcionando al mismo tiempo una mayor rigidez y capacidad de tensión. Además, la inhibición de NLRP3, un componente clave del inflamasoma involucrado en la regulación de la inflamación, en los adipocitos viscerales bloqueó significativamente la inflamación y la fibrosis, sugiriendo ser un potencial regulador del desarrollo de comorbilidades asociadas a la obesidad. En términos de factores inductores de la fibrosis, también mostramos el papel novedoso de la dermatopontina en la remodelación patológica de la MEC del TA en pacientes con obesidad. Finalmente, descubrimos que el cociente 22 Adiponectina/Leptina podría constituir un factor a tener en cuenta a la hora de evaluar la remisión de la diabetes tipo 2 tras la CB en pacientes con obesidad

Changes in adipose tissue plasticity after bariatric surgery and their role in the improvement of obesity-associated comorbidities

Adipose tissue (AT) is considered a plastic and dynamic endocrine organ with obesity driving changes in its biomechanical properties as well as in its extracellular matrix (ECM) remodelling, inflammation and mechanotransduction profiles, leading to the impairment of whole-body homeostasis. To achieve important and sustained weight loss as well as for the resolution of obesity-associated diseases, bariatric surgery (BS) is considered the most effective option in adequately selected patients. Despite great efforts to understand the processes involved in both, the development of dysfunctional AT and the favourable outcomes of BS, the underlying biological mechanisms have not been fully disentangled. Therefore, the objective of the present PhD thesis is to evaluate changes in AT plasticity together with their associations with the inflammation profile as well as ECM remodelling and mechanotransduction properties in an animal model of diet-induced obesity (DIO) and in patients with obesity. At the same time, we aimed to analyse the effect of BS on these biological processes, beyond the mere weight loss. We found that changes in the biomechanical properties of AT in obesity, including decreased Young’ modulus (E), ultimate tensile strength (UTS) and strain at UTS, were associated with the deterioration of body homeostasis. In this line, obesity induced changes in the inflammation, fibrosis and ECM remodelling profiles not only in AT but also in the liver being also related to the development of obesity comorbidities. Our findings also provide new insights into AT adaptation after BS beyond caloric restriction, being demonstrated by significant changes in the mechanotransduction and inflammatory profiles together with the decrease in the crosslinking and synthesis of collagens as well as an increase in its degradation. Our data also supports the notion that the higher blood vessel density found in AT after BS is involved in the increased E, UTS and strain at UTS values, providing at the same time higher stiffness and increased strain capacity. Furthermore, the inhibition of NLRP3, a key component of the inflammasome involved in the regulation of inflammation, in visceral adipocytes significantly blocked inflammation and fibrosis suggesting its potential to regulate the development of obesity-associated comorbidities. In terms of fibrosis-inducing factors, we also showed a novel role of dermatopontin in the pathological AT ECM remodelling during obesity. Finally, we proposed that the measurement of the Adiponectin/Leptin ratio after BS might constitute a significant factor for evaluating the remission of type 2 diabetes after bariatric procedures.El tejido adiposo (TA) es un órgano endocrino plástico y dinámico, que experimenta cambios en sus propiedades biomecánicas, así como en los perfiles de remodelación de su matriz extracelular (MEC), inflamación y mecanotransducción con la obesidad. La cirugía bariátrica (CB) constituye la opción más efectiva para lograr una pérdida de peso importante y sostenida en el tiempo, así como para la resolución de comorbilidades asociadas a la obesidad en pacientes adecuadamente seleccionados. A pesar de los grandes esfuerzos realizados para comprender los procesos involucrados tanto en el desarrollo del TA disfuncional como en los efectos favorables de la CB, no se han desentrañado completamente los mecanismos biológicos subyacentes. Por todo ello, el objetivo de la presente tesis doctoral es evaluar los cambios en la plasticidad del TA, además de estudiar su relación con el perfil inflamatorio, así como con el remodelado de la MEC y propiedades de mecanotransducción en un modelo animal de obesidad inducida por dieta (OID) y en pacientes con obesidad. Al mismo tiempo nos propusimos analizar el efecto de la CB sobre dichos procesos biológicos, más allá de la mera pérdida de peso. Nuestros resultados muestran que los cambios en las propiedades biomecánicas del TA en animales con obesidad, incluyendo la disminución del módulo de Young (E), la resistencia máxima a la tracción (RMT) y la tensión en RMT, se asociaron con el deterioro de la homeostasis corporal. En esta línea, la obesidad indujo cambios en los perfiles de inflamación, fibrosis y remodelado de la MEC no exclusivamente en el TA, sino también en el hígado, relacionándose también con el desarrollo de comorbilidades asociadas a la obesidad. Los datos obtenidos revelan nuevos hallazgos sobre la adaptación del TA tras CB más allá de la restricción calórica, demostrando cambios significativos en los perfiles inflamatorios y de mecanotransducción junto con la disminución en la conformación reticulada de colágenos y su síntesis, así como un aumento en su degradación. Nuestros resultados también respaldan la noción de que la mayor densidad de vasos sanguíneos encontrada en el TA tras CB está asociada con un aumento de E, RMT y tensión en RMT, proporcionando al mismo tiempo una mayor rigidez y capacidad de tensión. Además, la inhibición de NLRP3, un componente clave del inflamasoma involucrado en la regulación de la inflamación, en los adipocitos viscerales bloqueó significativamente la inflamación y la fibrosis, sugiriendo ser un potencial regulador del desarrollo de comorbilidades asociadas a la obesidad. En términos de factores inductores de la fibrosis, también mostramos el papel novedoso de la dermatopontina en la remodelación patológica de la MEC del TA en pacientes con obesidad. Finalmente, descubrimos que el cociente 22 Adiponectina/Leptina podría constituir un factor a tener en cuenta a la hora de evaluar la remisión de la diabetes tipo 2 tras la CB en pacientes con obesidad

Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements

Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improve- ments. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up- regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with en- hanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better character- ization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities

Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements

Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improve- ments. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up- regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with en- hanced blood vessel density providing, simultaneously, higher stiffness and more ductility. Statement of Significance Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity- associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better character- ization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities

Por una nueva globalización

El foco de interés de este número está centrado en el tema de la globalización, el cual ha sido tratado en los artículos de la sección Lente de Aproximación . La idea de “globalización” contiene una carga semántica absolutamente disímil para las personas dependiendo de donde estén ubicados, sea en el norte o en el sur de nuestro planeta, o en el norte o sur de nuestros países. Según algunos autores, implica para la mayoría dimensiones perversas y destructivas, mientras que otros piensan en las posibilidades que abre. Surgen así diversas interpretaciones, algunas de las cuales hemos querido mostrar en este número, buscando responder a preguntas como: ¿existe una “errónea” identificación de la globalización con el neoliberalismo? ¿son fenómenos separables? ¿es posible otra globalización? ¿qué se requiere para ello? ¿cuál globalización es compatible con la sustentabilidad, con la inclusión social y con la vida buena?, ¿qué novedad histórica representa la globalización