950 research outputs found

    E2F1, a Novel Regulator of Metabolism.

    Get PDF
    In the past years, several lines of evidence have shown that cell cycle regulatory proteins also can modulate metabolic processes. The transcription factor E2F1 is a central player involved in cell cycle progression, DNA-damage response, and apoptosis. Its crucial role in the control of cell fate has been extensively studied and reviewed before; however, here, we focus on the participation of E2F1 in the regulation of metabolism. We summarize recent findings about the cell cycle-independent roles of E2F1 in various tissues that contribute to global metabolic homeostasis and highlight that E2F1 activity is increased during obesity. Finally, coming back to the pivotal role of E2F1 in cancer development, we discuss how E2F1 links cell cycle progression with different metabolic adaptations required for cell growth and survival

    Cancer: Linking Powerhouses to Suicidal Bags.

    Get PDF
    Membrane-bound organelles are integrated into cellular networks and work together for a common goal: regulating cell metabolism, cell signaling pathways, cell fate, cellular maintenance, and pathogen defense. Many of these interactions are well established, but little is known about the interplay between mitochondria and lysosomes, and their deregulation in cancer. The present review focuses on the common signaling pathways of both organelles, as well as the processes in which they both physically interact, their changes under pathological conditions, and the impact on targeting those organelles for treating cancer

    Estudi de les accions del vent sobre una coberta corbada mitjançant simulació numèrica

    Get PDF
    Aquest projecte té l’origen en el càlcul dels esforços que fa el vent sobre una coberta corba d’una pista de pàdel suportada per pilars per tal de fer-ne el seu dimensionament. Un dels inconvenients que troben els enginyers d’estructures a l’hora de dissenyar-ho, és que la norma vigent sobre aquest tipus de construccions no especifica la distribució de pressions sobre la coberta de pàdel formada per una marquesina en forma de làmina corba. Amb l’objectiu d’assentar les bases per a la determinació de la distribució de pressions sobre la marquesina, es vol comprovar si la simulació numèrica amb computador de fluids pot servir com a alternativa a la normativa. Per tant, s’ha identificat un cas similar corresponent a una coberta que consta d’un sostre idèntic, però suportat per dues parets laterals que sí que s’inclou a la normativa. L’objectiu bàsic ha sigut comprovar si s’arriba als mateixos resultats tant per normativa com per simulació. Per tant, en primer lloc s’han determinat les característiques del vent que considera necessari tenir en compte la normativa si es vol instal·lar la coberta a Catalunya. A continuació, s’ha procedit a desenvolupar el model numèric en base a aquestes condicions. Per portar-ho a terme s’ha hagut de generar la geometria d’estudi, el seu volum de control, el seu mallat i s’han aplicat les condicions de contorn durant la simulació. D’aquests passos, mallar el sòlid ha estat el que ha comportat més problemes ja que la geometria no permetia fer un mallat qualsevol. Finalment, s’han simulat els diferents casos i s’han comparat els resultats numèrics amb els proporcionats per la normativa per treure’n les conclusions pertinents. Tenint en compte els errors obtinguts amb les diferents simulacions, s’ha pogut determinar que el millor model per fer aquestes simulacions era tenir un perfil de velocitats no uniforme. Pel que fa la turbulència, no ha estat una variable que fes variar en excés els resultats. Donada la bona concordança entre simulació i normativa obtinguda en el nostre cas, ara el següent pas seria simular la coberta sense parets de sustentació, amb l’objectiu d’obtenir uns resultats coherents tenint en compte els aconseguits amb el model anterior

    CDK4, a new metabolic sensor that antagonizes AMPK.

    Get PDF
    Cyclin-dependent kinase 4 (CDK4) is a positive regulator of cell cycle progression, however, there is growing evidence demonstrating that its function exceeds the control of cell division. Here we show that CDK4 is an important regulator of cellular substrate utilization through direct inhibition of the metabolic regulator AMPK (AMP-activated protein kinase)

    Chromatin immunoprecipitation improvements for the processing of small frozen pieces of adipose tissue.

    Get PDF
    Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue. Here, we optimize the standard protocol of ChIP for small pieces of frozen human adipose tissue. In addition, we test ChIP for the histone mark H3K4m3, which is related to active promoters, and validate the performance of the ChIP by analyzing gene promoters for factors usually studied in adipose tissue using qPCR. Our improvements result in a higher performance in chromatin shearing and DNA recovery of adipocytes from the tissue, which may be useful for ChIP-qPCR or ChIP-seq analysis

    The Retinoblastoma-Histone Deacetylase 3 Complex Inhibits PPARγ and Adipocyte Differentiation

    Get PDF
    AbstractThe retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP). We show here that the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor pivotal for adipogenesis, promotes adipocyte differentiation more efficiently in the absence of RB. PPARγ and RB were shown to coimmunoprecipitate, and this PPARγ-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPARγ's capacity to drive gene expression and adipocyte differentiation. Dissociation of the PPARγ-RB-HDAC3 complex by RB phosphorylation or by inhibition of HDAC activity stimulates adipocyte differentiation. These observations underscore an important function of both RB and HDAC3 in fine-tuning PPARγ activity and adipocyte differentiation

    Interventions to facilitate shared decision-making using decision aids with patients in Primary Health Care: A systematic review

    Get PDF
    BACKGROUND: Shared decision making (SDM) is a process within the physician-patient relationship applicable to any clinical action, whether diagnostic, therapeutic, or preventive in nature. It has been defined as a process of mutual respect and participation between the doctor and the patient. The aim of this study is to determine the effectiveness of decision aids (DA) in primary care based on changes in adherence to treatments, knowledge, and awareness of the disease, conflict with decisions, and patients'' and health professionals'' satisfaction with the intervention. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in Medline, CINAHL, Embase, the Cochrane Central Register of Controlled Trials, and the NHS Economic Evaluation Database. The inclusion criteria were randomized clinical trials as study design; use of SDM with DA as an intervention; primary care as clinical context; written in English, Spanish, and Portuguese; and published between January 2007 and January 2019. The risk of bias of the included studies in this review was assessed according to the Cochrane Collaboration''s tool. RESULTS: Twenty four studies were selected out of the 201 references initially identified. With the use of DA, the use of antibiotics was reduced in cases of acute respiratory infection and decisional conflict was decreased when dealing with the treatment choice for atrial fibrillation and osteoporosis. The rate of determination of prostate-specific antigen (PSA) in the prostate cancer screening decreased and colorectal cancer screening increased. Both professionals and patients increased their knowledge about depression, type 2 diabetes, and the perception of risk of acute myocardial infarction at 10 years without statins and with statins. The satisfaction was greater with the use of DA in choosing the treatment for depression, in cardiovascular risk management, in the treatment of low back pain, and in the use of statin therapy in diabetes. Blinding of outcomes assessment was the most common bias. CONCLUSIONS: DA used in primary care are effective to reduce decisional conflict and improve knowledge on the disease and treatment options, awareness of risk, and satisfaction with the decisions made. More studies are needed to assess the impact of shared decision making in primary care

    INTERVENCIONES PARA LLEVAR A CABO LAS DECISIONES COMPARTIDAS EN ATENCIÓN PRIMARIA

    Get PDF
    RESUMEN ANTECEDENTES La toma de decisiones compartidas (TDC) es una forma de relación médico paciente aplicable a cualquier acto clínico, concretamente, cuando existe incertidumbre científica sobre los resultados de las diferentes opciones diagnósticas, terapéuticas y/o profilácticas. Se ha estudiado en enfermedades crónicas (elección de estilos de vida, adherencia al tratamiento), cáncer (mama, próstata), y en cuidados paliativos. Se encuadra en la llamada “atención centrada en el paciente” que implica organizar la atención a la salud pensando en los pacientes en vez de en los profesionales que la facilitan; las decisiones se adoptan de manera conjunta entre el equipo médico y el paciente, una vez que el paciente dispone de la información necesaria. OBJETIVOS Evaluar la efectividad de la toma de decisiones compartidas en las consultas de Atención Primaria en cuanto a los resultados clínicos, adherencia a los tratamientos, conflicto con las decisiones, satisfacción de profesionales y pacientes con el proceso y conocimiento de los pacientes sobre su enfermedad MÉTODO Se ha llevado a cabo una revisión sistemática de 104 artículos publicados en MEDLINE, CENTRAL y NHS, con diseño ensayo clínico aleatorizado controlado. Publicados en Inglés o Español o portugués. RESULTADOS De los 51 ensayos revisados, 28 han obtenido resultados clínicos estadísticamente significativos, principalmente en intensificación del tratamiento y en el cribado poblacional de cáncer de próstata y colorrectal en las consultas de Atención Primaria. Hubo diferencias significativas, mejorando la eficacia de las decisiones y disminuyendo el conflicto decisional en 7 artículos. En 14 estudios hubo una mayor satisfacción con la intervención que aplica las decisiones compartidas La adherencia al tratamiento no ha presentado resultados estadísticamente significativos. En 9 estudios los pacientes refieren una mejoría en el conocimiento de la medicación y de la propia enfermedad, percibiendo una mayor eficacia en la toma de decisiones. CONCLUSIONES La TDC es importante como nuevo modelo de relación médico-paciente, sobretodo en el ámbito de la Atención Primaria por el alto nivel de incertidumbre que la caracteriza, habiendo mostrado ser efectiva en el cribado de cáncer de próstata y en los conflictos derivados de la prescripción de antibióticos principalmente. No podemos concluir acerca de la efectividad de la TDC en las enfermedades estudiadas, para lo que será necesario realizar más estudios

    Anàlisi Financera dels aeroports d'AENA Aeropuertos SA

    Get PDF
    BibliografiaEl Grup Aena va dividir-se en dues unitats de negoci l'any 2010 per a millorar la gestió aeroportuària al separar-la de la de navegació. El deute del d'Aena Aeropuertos SA ha augmentat un 16% en els darrers 5 anys, i la privatització parcial de l'Ens Públic és una opció que es veu cada vegada més propera. L'esclat de la crisis econòmica del país l'any 2008 va afectar significativament la rendibilitat de les inversions portades a terme en el període 2000-2010, fent que 4 anys després es qüestionin els arguments que les van sustentar. Aquest treball persegueix l'anàlisi d'aquestes inversions i la seva rendibilitat a través de l'estudi dels resultats globals i individuals de cada aeroport. Es planteja des d'una òptica temporal, que contempla l'evolució del Grup Aena i dels aeroports al llarg dels darrers anys.El Grupo AENA se dividió en dos unidades de negocio el año 2010 para mejorar su gestión aeroportuaria al separarla de la de navegación. La deuda de AENA Aeropuertos SA ha aumentado un 16% en los últimos 5 años, y la privatización parcial del Ente Público es una opción que se ve cada vez más cercana. El inicio de la crisis económica del país el año 2008 afectó significativamente la rentabilidad de las inversiones llevadas a cabo en el periodo 2000-2010, haciendo que 4 años más tarde se cuestionen los argumentos que las sustentaron. Este trabajo persigue el análisis de estas inversiones y su rentabilidad a través del estudio de los resultados globales e individuales de cada aeropuerto. Se plantea desde una óptica temporal, que contempla la evolución del Grupo AENA y de sus aeropuertos a lo largo de los últimos años.The Aena Group was divided into two business units in 2010 in order to improve its airport management by separating it from navigation management. Aena Aeropuertos SA's debt has increased by 16% in the last 5 years, and a partial privatization of the public body seems more and more likely with each passing day. The outbreak of the economic crisis in Spain in 2008 significantly affected the profitability of the investments made during the 2000-2010 period, and now, 4 years later, the rationale behind them is being questioned. This project analyses these investments and their profitability by studying both the global and individual results of each airport, and examines the development of the Aena Group and their airports over the last few years
    corecore