IGF binding protein‐6 expression in vascular endothelial cells is induced by hypoxia and plays a negative role in tumor angiogenesis

Hypoxia stimulates tumor angiogenesis by inducing the expression of angiogenic molecules. The negative regulators of this process, however, are not well understood. Here, we report that hypoxia induced the expression of insulin‐like growth factor binding protein‐6 (IGFBP‐6), a tumor repressor, in human and rodent vascular endothelial cells (VECs) via a hypoxia‐inducible factor (HIF)‐mediated mechanism. Addition of human IGFBP‐6 to cultured human VECs inhibited angiogenesis in vitro . An IGFBP‐6 mutant with at least 10,000‐fold lower binding affinity for IGFs was an equally potent inhibitor of angiogenesis, suggesting that this action of IGFBP‐6 is IGF‐independent. The functional relationship between IGFBP‐6 and vascular endothelial growth factor (VEGF), a major hypoxia‐inducible angiogenic molecule, was examined. While VEGF alone increased angiogenesis in vitro , co‐incubation with IGFBP‐6 abolished VEGF‐stimulated angiogenesis. The in vivo role of IGFBP‐6 in angiogenesis was tested in flk1 :GFP zebrafish embryos, which exhibit green fluorescence protein in developing vascular endothelium, permitting visualization of developing blood vessels. Injection of human IGFBP‐6 mRNA reduced the number of embryonic inter‐segmental blood vessels by ∼40%. This anti‐angiogenic activity is conserved in zebrafish because expression of zebrafish IGFBP‐6b had similar effects. To determine the anti‐angiogenic effect of IGFBP‐6 in a tumor model, human Rh30 rhabdomyosarcoma cells stably transfected with IGFBP‐6 were inoculated into athymic BALB/c nude mice. Vessel density was 52% lower in IGFBP‐6‐transfected xenografts than in vector control xenografts. These results suggest that the expression of IGFBP‐6 in VECs is up‐regulated by hypoxia and IGFBP‐6 inhibits angiogenesis in vitro and in vivo .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90159/1/26201_ftp.pd

Prediction of The High Voltage Insulators Service Life Based on The Effective Values of Leakage Currents

The insulation condition of overhead lines is one of the main factors affecting reliability of overhead power transmission lines. It is known that the process of insulation lapping or rupture is mainly affected by environmental conditions and the degree of pollution of the insulators surface. This paper substantiates the possibility of using the leakage current values of insulators for monitoring the state of insulation and predicting its resource. The results of experimental studies of leakage currents of high-voltage insulators depending on their service life are given, on the basis of which forecasting the possible resource of insulators is carried out. The results obtained can be used to develop more effective diagnostics for detecting insulator failures at an early stage to take appropriate measures to coordinate the insulation

Răzvan Bran: Las oraciones subordinadas y las construcciones sintácticas complejas en español. Consideraciones teóricas y ejercicios prácticos

Review of the book Subordinate Sentences and Complex Syntactic Constructions in Spanish. Theoretical Considerations and Practical Exercises by Răzvan Bran.Reseña del libro Las oraciones subordinadas y las construcciones sintácticas complejas en español. Consideraciones teóricas y ejercicios prácticos de Răzvan Bran

Estudio comparativo in vitro de la profundidad de polimerización de resinas compuestas fluidas polimerizadas por luz L.E.D. versus luz halógena, a través de resinas compuestas previamente endurecidas

Trabajo de Investigación Requisito para optar al Título de Cirujano DentistaEn este estudio in-vitro se comparó la profundidad de polimerización de una resina compuesta fluida al ser foto polimerizada a través de cuerpos de resina indirecta de 3mm y 4mm mediante una lámpara LED y una lámpara halógena convencional. Para esto se fueron conformados 4 grupos experimentales Un primer grupo compuesto por 15 muestras de resina compuesta fluida WAVE lv (SDI) color A3 polimerizados en un formador metálico a través de 3mm. de resina indirecta Art-Glass (Heraeus Kulzer, Germany, color A3) con una lámpara LED (Radii-Cal SDI, Australia) por 40 segundos. Un segundo grupo de 15 muestras de resina fluida polimerizada a través de 3mm de resina indirecta por 40 segundos con una lámpara halógena convencional de cuarzo tungsteno (Elipar™ 2500 3m ESPE, St. Paul, U.S.A.). Un tercer grupo de 15 muestras de resina compuesta fluida polimerizadas en un formador metálico a través de 4mm. de resina indirecta con una lámpara LED por 40 segundos. Un cuarto grupo de 15 muestras de resina compuesta fluida polimerizadas en un formador metálico a través de 4mm. de resina indirecta con una lámpara halógena convencional de cuarzo tungsteno por 40 segundos. Y dos grupos control uno consistente en 8 muestras de resina fluida polimerizadas en un formador metálico directamente con una lámpara LED por 40 segundos y 8 muestras de resina fluida polimerizadas en un formador metálico directamente con una lámpara halógena convencional de cuarzo tungsteno por 40 segundos. Las 76 muestras una vez polimerizadas fueron retiradas del formador metalico y se les retiró la resina sin polimerizar una espátula plástica. Fueron entonces medidas con un micrómetro con una sensibilidad de 0.01mm. los valores obtenidos fueron divididos en 2 de acuerdo a la norma ISO:4049:2009., y tabulados. Se realizó el análisis estadístico y los datos fueron comparados mediante un test ANOVA con corrección de Bonferroni que arrojó diferencias significativas para todos los grupos en estudio salvo los grupos control. Se concluyó entonces que al aumentar el espesor de la resina indirecta interpuesta disminuye el valor de profundidad de polimerización obtenido. Además se concluyó que es posible lograr una mayor profundidad de polimerización de la resina compuesta fluida mediante la unidad LED respecto a la unidad halógena convencional al interponer cuerpos de resina indirecta de 3 y 4 mm y que esta diferencia es estadísticamente significativa (p<0,05) Además la profundidad de polimerización para ambos grupos polimerizados a través de cuerpos de resina indirecta de 4mm fue insuficiente según la norma ISO:4049:2009 por lo que podría ser necesario aumentar el tiempo de polimerización para obtener una profundidad de curado adecuada con estructuras de resina indirecta de espesores mayores a 3m

Realidad virtual en videojuegos como una herramienta para promover la actividad turística en Lima – Perú

El proyecto consiste en el desarrollo de un videojuego en Realidad Virtual en el cual se modela y muestra una referencia de un lugar turístico con un diseño 3D. Este software tiene como objetivo promover la actividad turística en Lima – Perú mediante la didáctica interacción con el escenario. Durante el desarrollo del sistema se utilizó la metodología CASCADA (Análisis, Diseño, Implementación, Pruebas y Mantenimiento). En el software, el usuario podrá recorrer un espacio (escenario), teniendo como objetivo completar los puntos para terminar el nivel satisfactoriamente. Al finalizar el desarrollo, el software se le mostrará al público en la web y aplicativo móvil, el cual se le pondrá el instalador en el equipo del usuario que desea probarlo.Trabajo de investigaciónCampus Lima Centr

The transient receptor potential vanilloid 4 channel modulates uterine tone during pregnancy

The importance of gaining insight into the mechanisms underlying uterine quiescence and contractility is highlighted by the absence of an effective strategy to prevent or treat preterm labor, the greatest cause of perinatal mortality and morbidity worldwide. Although current evidence suggests that in myometrial smooth muscle cells (mSMCs) calcium homeostasis is modulated near term to promote uterine contractility, the efficacy of blocking voltage-operated calcium channels is limited by dose-related cardiovascular side effects. Thus, we considered whether uterine contractility might be modulated by calcium entry via transient receptor potential vanilloid 4 (TRPV4) channels. In mSMC, TRPV4 gene and protein expression increased with gestation, and TRPV4-mediated Ca2+ entry and contractility were increased in mSMC from pregnant compared to nonpregnant rats. Cell membrane TRPV4 expression was specifically increased, whereas the expression of β-arrestin-1 and β-arrestin-2, molecules that can sequester TRPV4 in the cytoplasm, decreased. Physical interaction of β-arrestin-2 and TRPV4 was apparent in nonpregnant, but absent in pregnant, mouse uterus. Moreover, direct pharmacologic activation of TRPV4 increased uterine contraction, but oxytocin-induced myometrial contraction was blocked by pharmacologic inhibition of TRPV4 and decreased in mice with global deletion of TRPV4. Finally, TRPV4 channel blockade prolonged pregnancy in two distinct in vivomurinemodels of preterm labor, whereas the absence of either β-arrestin-1 or β-arrestin-2 increased susceptibility to preterm labor. These data suggest that TRPV4 channel activity modulates uterine contractility and might represent a therapeutic target to address preterm labor

Purification and characterization of native human insulin-like growth factor binding protein-6

Insulin-like growth factor binding proteins (IGFBPs) are key regulators of insulin-like growth factor (IGF) mediated signal transduction and thereby can profoundly influence cellular phenotypes and cell fate. Whereas IGFBPs are extracellular proteins, intracellular activities were described for several IGFBP family members, such as IGFBP-3, which can be reinternalized by endocytosis and reaches the nucleus through routes that remain to be fully established. Within the family of IGFBPs, IGFBP-6 is unique for its specific binding to IGF-II. IGFBP-6 was described to possess additional IGF-independent activities, which have in part been attributed to its translocation to the nucleus; however, cellular uptake of IGFBP-6 was not described. To further explore IGFBP-6 functions, we developed a new method for the purification of native human IGFBP-6 from cell culture supernatants, involving a four-step affinity purification procedure, which yields highly enriched IGFBP-6. Whereas protein purified in this way retained the capacity to interact with IGF-II and modulate IGF-dependent signal transduction, our data suggest that, unlike IGFBP-3, human IGFBP-6 is not readily internalized by human tumor cells. To summarize, this work describes a novel and efficient method for the purification of native human insulin-like growth factor binding protein 6 (IGFBP-6) from human cell culture supernatants, applying a four-step chromatography procedure. Intactness of purified IGFBP-6 was confirmed by IGF ligand Western blot and ability to modulate IGF-dependent signal transduction. Cellular uptake studies were performed to further characterize the purified protein, showing no short-term uptake of IGFBP-6, in contrast to IGFBP-3

Efficacy of non-pharmacological interventions to treat malnutrition in older persons : A systematic review and meta-analysis. The SENATOR project ONTOP series and MaNuEL Knowledge Hub project

The preparation of this paper was supported by the MalNutrition in the ELderly (MaNuEL) knowledge hub. MaNuEL is supported by the Joint Programming Initiative ‘Healthy Diet for a Healthy Life’. The MaNuEL funding agencies supporting this paper are (in alphabetical order of participating Member State): France: Ecole Supérieure d’Agricultires (ESA); Germany: Federal Ministry of Food and Agriculture (BMEL) represented by Federal Office for Agriculture and Food (BLE); The Netherlands: The Netherlands Organisation for Health Research and Development (ZonMw). This work was also supported by the SENATOR trial (FP7-HEALTH-2012-305930).Peer reviewedPostprin

Conflicting Climate Change Frames in a Global Field of Media Discourse

Reducing global emissions will require a global cosmopolitan culture built from detailed attention to conflicting national climate change frames (interpretations) in media discourse. The authors analyze the global field of media climate change discourse using 17 diverse cases and 131 frames. They find four main conflicting dimensions of difference: validity of climate science, scale of ecological risk, scale of climate politics, and support for mitigation policy. These dimensions yield four clusters of cases producing a fractured global field. Positive values on the dimensions show modest association with emissions reductions. Data-mining media research is needed to determine trends in this global field.Peer reviewe