Design, synthesis, in vitro, in vivo and in silico pharmacological characterization of antidiabetic N-Boc-l-tyrosine-based compounds

Abstract In this study, we synthesized five N-Boc-L-tyrosine-based analogues to glitazars. The in vitro effects of compounds 1–5 on protein tyrosine phosphatase 1B (PTP-1B), peroxisome proliferator-activated receptor alpha and gamma (PPARα/γ), glucose transporter type-4 (GLUT-4) and fatty acid transport protein-1 (FATP-1) activation are reported in this paper. Compounds 1 and 3 were the most active in the in vitro PTP-1B inhibition assay, showing IC50s of approximately 44 μM. Treatment of adipocytes with compound 1 increased the mRNA expression of PPARγ and GLUT-4 by 8- and 3-fold, respectively. Moreover, both compounds (1 and 3) also increased the relative mRNA expression of PPARα (by 8-fold) and FATP-1 (by 15-fold). Molecular docking studies were performed in order to elucidate the polypharmacological binding mode of the most active compounds on these targets. Finally, a murine model of hyperglycemia was used to evaluate the in vivo effectiveness of compounds 1 and 3. We found that both compounds are orally active using an exploratory dose of 100 mg/kg, decreasing the blood glucose concentration in an oral glucose tolerance test and a non-insulin-dependent diabetes mellitus murine model. In conclusion, we demonstrated that both molecules showed strong in vitro and in vivo effects and can be considered polypharmacological antidiabetic candidates

Origin and driving mechanisms of marine litter in the shelf-incised Motril, Carchuna, and Calahonda canyons (northern Alboran Sea)

Introduction and methodsMarine litter density, distribution and potential sources, and the impact on canyon seafloor habitats were investigated in the Motril, Carchuna and Calahonda canyons, located along the northern margin of the Alboran Sea. During the ALSSOMAR-S2S oceanographic survey carried out in 2019, canyon floor imagery was collected by a Remotely Operated Vehicle along 5 km in the Motril Canyon, 10 km in the Carchuna Canyon, and 3 km in Calahonda Canyon, together with 41 surficial sediment samples. Additionally, coastal uses, maritime traffic and fishing activity data were analyzed. A 50 m resolution multibeam bathymetry served as base map. ResultsIn the Motril and Calahonda canyons, the density of marine litter was low and the material was dispersed, very degraded and partially buried. In contrast, the Carchuna Canyon contained a greater amount and variety of litter. The Carchuna Canyon thalweg exhibited a density of marine litter up to 8.66 items center dot 100 m(-1), and litter hotspots with a density of up to 42 items center dot m(2) are found along the upper reaches of the canyon thalweg. DiscussionLow litter abundances found in the studied canyons most likely reflect low population densities and the absence of direct connections with streams in the nearby coasts. The high shelf incision of the Carchuna Canyon and its proximity to the coastline favor littoral sediment remobilization and capture as well as the formation of gravity flows that transport the marine litter along the thalweg toward the distal termination of the channel. Litter hotspots are favored by the canyon morphology and the occurrence of rocky outcrops. Most debris is of coastal origin and related to beach occupation and agricultural practices in the adjacent coastal plain. A third origin was represented by fishing gear in the study area. Fishing activity may be producing an impact through physical damage to the skeletons of the colonial scleractinians located in the walls of the Carchuna Canyon. In contrast, the Motril and Calahonda canyons can be considered passive systems that have mainly acted as depositional sinks in the recent past, as evidenced by buried marine litter.18-ESMARES2-CIRCA project of the Instituto Español de Oceanografıa; DL57/2016/CP1361/CT0009info:eu-repo/semantics/publishedVersio

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 10

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 10, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Healthy thalli of the invasive seaweed Rugulopteryx okamurae (Phaeophyceae) being massively dragged into deep-sea bottoms by the Mediterranean Outflow Water

The invasive seaweed Rugulopteryx okamurae has recently arrived in Europe from the western Pacific. Its explosive spread on coastal areas of the Gulf of Cádiz (GoC), Strait of Gibraltar and Alboran Sea is spoiling native coastal ecosystems and inflicting heavy losses on ecosystem services. We discovered for the first time large amounts (up to 17 g m) of detached R. okamurae thalli on deep-sea bottoms of the GoC that are being dragged from the Strait of Gibraltar shores into the NE Atlantic by the Mediterranean Outflow Water (MOW). Laboratory experiments revealed that collected unattached macroalgae from deep-sea locations were alive and healthy and maintained intact photosynthetic capacity after long dark periods, suggesting a tremendous resilience and invasive potential. Given the rapid transport of healthy thalli by the MOW and massive accumulation of them in the GoC basin, R. okamurae could represent a major threat to NE Atlantic ecosystems, affecting not only coastal but also deep-sea habitats.Funding was provided by the projects INPULSE (CTM2016-75129-C3-1-R) and ESMARES-2, both with financial support from Ministerio de Transición Ecológica and Reto Demográfico (MITECO) and LIFE IP PAF INTEMARES, coordinated by the Fundación Biodiversidad of the Ministerio de Transición Ecológica and Reto Demográfico, with financial support from the European Union’s LIFE programme (LIFE15 IPE ES 012)

Financial Stability Report - March 2009

Durante 2008 la economía mundial entró en un período de recesión económica como resultado de la crisis financiera internacional. El panorama de crecimiento de las economías desarrolladas en 2009 y 2010 es pesimista. Las menores exportaciones, la caída en las remesas y la disminución de los flujos de capital hacia América Latina, incluida Colombia, tendrán un impacto negativo sobre el sector real, reflejado en bajas tasas de crecimiento y mayor desempleo. Si bien el efecto de la crisis sobre el sistema financiero colombiano ha sido moderado, gracias a la a las medidas monetarias y cambiarias adoptadas por la Junta Directiva del Banco de la República y a la baja exposición de las entidades a los activos “tóxicos”, el tiempo de duración de la crisis podría aumentar la vulnerabilidad de los intermediarios. Sin embargo, la solidez exhibida por el sistema financiero colombiano, en particular la de los bancos comerciales, ayuda a amortiguar los efectos negativos del mayor riesgo crediticio.The world economy entered a period of recession during 2008 as a result of the international financial crisis. The outlook for growth in the developed economies during 2009 and 2010 is pessimistic. Fewer exports, fewer remittances and the decline in capital flows to Latin America, including Colombia, will have a negative impact on the productive sector, reflected in low growth rates and higher unemployment. Although the impact of the crisis on Colombia’s financial system has been moderate, due to the monetary and exchange measures adopted by the Board of Directors of Banco de la República and owing to the system’s limited exposure to toxic assets, the length of the crisis could make intermediaries more vulnerable. However, the country’s financial system has shown itself to be sound, particularly the commercial banks. This will help to cushion the negative effects of additional credit risk

El eterno retorno del populismo en América Latina y el Caribe

Este libro reúne las ponencias del seminario Nuevas formas de democracia (CLACSO, 2007) y del coloquio Nuevos y viejos populismos (Universidad Javeriana y Goethe Institut, 2008). En total son 23 autores que reflexionan, plantean ideas teóricas y hacen estudios de caso específicos relacionados con la democracia, el populismo y el pluralismo en varios países de América Latina durante el siglo XX y en algunas de las políticas actuales.Bogot

El eterno retorno del populismo en América Latina y el Caribe

En los años ochenta la mayoría de los países latinoamericanos hizo la transición a la democracia después de décadas de autoritarismo. Casi inmediatamente, y con visiones no muy optimistas, la academia se ocupó de las posibilidades de consolidación democrática de los nuevos regímenes. Algunos como Juan Linz y Arturo Valenzuela se centraron en el tema del presidencialismo para señalar que este favorecía una lógica de suma cero en la que el ganador de las presidenciales "se llevaba todo", y que la rigidez del periodo presidencial y la doble legalidad producto de las elecciones separadas del Ejecutivo y del Legislativo, podían conducir a una parálisis del sistema que se resolviera en clave autoritaria, como fue el caso de Chile en 1973. Esta visión pesimista del futuro del presidencialismo latinoamericano solo comenzó a disiparse en los años noventa con los trabajos de Dieter Nohlen y Scott Mainwaring entre otros, y hoy algunos teóricos estudian las distintas formas como se resuelven las crisis presidenciales mostrando que ellas no conducen necesariamente a regímenes autoritarios y que antes bien, la salida del presidente puede ser una válvula de escape para salvar la democracia. (...

Financial Stability Report - September 2009

Durante el primer semestre de 2009 la economía mundial continuó experimentando los efectos de la crisis financiera internacional, aunque algunos indicadores, como el de aversión al riesgo y el crecimiento de la cartera del sector privado, registraron mejorías. En el caso de la economía colombiana, los índices de confianza del consumidor y el de expectativas para la industria y el comercio presentaron una leve recuperación, aunque siguen manteniendo niveles bajos. La mejor dinámica de la economía tendrá efectos positivos sobre el comportamiento de los riesgos del sistema financiero, la situación fiscal y el empleo. A junio de 2009 la cartera bruta del sistema financiero colombiano continuó desacelerándose (7,3% real anual frente a 12,9% un año antes), especialmente la de consumo que registró un crecimiento real anual de -0,5%, mientras que un año atrás creció 13,7%. Por su parte, la cartera comercial aumentó 11,4% y la hipotecaria con titularizaciones se incrementó en 6,6% real anual. Las inversiones de los establecimientos de crédito presentaron un repunte significativo al crecer a una tasa real anual de 23,8% frente a -4,6% en junio de 2008. Este comportamiento se explica tanto por el aumento en las nuevas tenencias de títulos de deuda pública, así como por sus valoraciones, las cuales se han presentado conjuntamente con las del mercado accionario.During the first half of 2009, the world economy continued to experience the effects of the international financial crisis, although some indicators, such as those denoting risk aversion and private sector loan portfolio growth, have improved. In the case of the Colombian economy, the consumer confidence index and the expectation index for industry and commerce demonstrated some recovery, but are still at low levels. More momentum in the economy will have a positive impact on risks to the financial system, the fiscal situation and employment. The slowdown in the gross loan portfolio held by the Colombian financial system continued in June 2009 (7.3% real annual growth compared to 12.9% the year before), especially consumer lending, which posted -0.5% real annual growth, as opposed to 13.7% a year earlier. On the other hand, the commercial loan portfolio was up 11.4% and mortgage loans, with securitization, registered a real annual increase of 6.6%. Credit institution investment rose considerably, at a real annual rate of 23.8% as opposed to -4.6% in June 2008. This performance explains much of the increase in new holdings of government bonds and their valuation, which occurred in conjunction with the stock market valuations