Comparative study of dopaminergic activity of tetrahydro-1H-[3]-benzazepines and their precursors

The discovery of the tetrahydro-1H-[3]-benzazepine SCH23390 [1], represented one of the most important advances in the study of dopaminergic receptors due to their behavior as a selective D1 receptor antagonist. The high affinity and selectivity of this tetrahydro-1H-[3]-benzazepine has led to the search for new structures because of their potential dopaminergic activity, especially 1-aryl-substituted tetrahydro-1H-[3]-benzazepines. Furthermore, their precursors, the tetrahydroisoquinolines 1-substituted have shown to have activity for D1 and D2 dopaminergic receptors.[2] We have carried out the synthesis of tetrahydro-1H-[3]-benzazepines 1,2-di-substituted by Stevens rearrangement (SR) on tetrahydroisoquinolinium salts. Stevens rearrangement is an efficient regio- and diastereoselective synthetic methodology. [3a,b] As part of our studies, we have performed the synthesis of benzazepines with modifications at the C-1 and C-2 positions with chlorine and hydroxyl groups at A-ring which is an important factor to modulate affinity at dopaminergic receptors. The interaction of these molecules with D1 and D2 dopaminergic receptors have been studied to establish a structure-activity relationship by radioligand binding assays.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Changes in macrofauna bioturbation during repeated heatwaves mediate changes in biogeochemical cycling of nutrients

The increasing frequency and intensity of marine heatwaves (MHWs) observed worldwide entails changes in the structure and functioning of ecological communities. While severe and extreme heatwaves often have more destructive effects, the more subtle effects of moderate and strong heatwaves may nevertheless affect ecosystem functioning through complex, context-dependent linkages between different processes. Here we conducted a laboratory experiment to study the effects of repeated short-term, strong MHWs on macrofauna bioturbation and associated solute fluxes as a measure of ecosystem functioning using natural soft-sediment communities from the Baltic Sea. Our results showed changes in both bioturbation and biogeochemical cycling of nutrients following short-term, strong heatwaves, which seemed to contribute to an enhanced degradation of organic matter in the seafloor and an enhanced exchange of solutes across the sediment-water interface as well as increased sediment oxygen consumption. Following changes in these processes, the relative contribution of macrofauna and the environmental context to ecosystem functioning was altered. Our results highlight the potential of even shorter-term, strong MHWs of having system-wide impacts due to changes in the mechanistic process of bioturbation underpinning the biogeochemical cycling of nutrients. This study also highlights the need to measure a wide range of variables for a comprehensive understanding of the changes in functioning under disturbances, such as MHWs.Peer reviewe

Spatiotemporal changes in surface sediment characteristics and benthic macrofauna composition off the Rhône River in relation to its hydrological regime

International audienceThe consequences of changes in the water flow of the Rhône River on surface sediment characteristics and benthic macrofauna composition were assessed within 3 distinct areas: (1) the delta front, (2) the prodelta, and (3) the distal zone. Five stations were sampled during or closely after: (1) an oceanic flood (April 2007), (2) a generalized flood (May 2008), (3) a Cevenol flood (December 2008), and (4) a dry period (July 2011). Measurements of sediment characteristics included granulometry (D0.5), bulk descriptors of sedimentary organics (OC, TN and THAA), descriptors of labile components of sedimentary organics (chloropigments, EHAA), and both descriptors of origin (Chl-b/Chl-a, C/N) and lability (Chl-a/(Chl-a+Phaeo-a), EHAA/THAA) of sedimentary organics. Sediment Profile Images were collected during April 2007, May 2008 and July 2011. Temporal changes in both sedimentary organics and benthic macrofauna were more important in the delta front and the prodelta than in the distal zone. Bulk characteristics of sedimentary organics presented decreasing inshore/offshore gradients during both April 2007 and July 2011 but not during May and December 2008. There were significant temporal changes in EHAA/THAA at all stations. Changes in benthic macrofauna composition differed between: (1) the delta front and the prodelta, and (2) the distal zone. In the former area, the dry period was associated with establishing a mature community characterized by high abundances and species richness. The best description of spatiotemporal changes in benthic macrofauna composition by surface sediment characteristics was obtained using D0.5, Chl-b/Chl-a, Chl-a/(Chl-a+Phaeo-a) and EHAA, which supports the role of the quality of sedimentary organics in controlling benthic macrofauna composition

Insulin-like growth factor II neuroprotective effects against mitochondrial-oxidative and neuronal damage induced by CORT and MPP+ in dopaminergic neurons

Aims: Parkinson’s disease (PD) affects 1–3% of the population aged over 65. Stress seems to contribute to PD neuropathology, probably by dysregulation of the hypothalamic–pituitary–adrenal axis. Key factors are oxidative stress, mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. Insulin-like growth factor II (IGF-II) has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Therefore, our aim was to study IGF-II protective effects against oxidative damage on a cellular combined model of PD and mild to moderate stress, based on corticosterone (CORT) and the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Methods: The dopaminergic neuronal cell line SN4741 (RRID:CVCL_S466) derived from mouse substantia nigra were exposed to 200 μM MPP+, 0.5 μM CORT or both, with or without 25 ng/mL IGF-II, for 2.5 or 6 h. Cell viability, oxidative stress parameters, mitochondrial and dopamine markers and intracellular signaling pathways were evaluated. Results: The administration of MPP+ or CORT individually led to cell damage compared to control situations, whereas the combination of both drugs produced very considerable toxic synergistic effect. IGF-II counteracts the mitochondrial-oxidative damage, protecting dopaminergic neurons from death and neurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. Conclusions: IGF-II capacity to protect nigral dopamine neurons against mitochondrial-oxidative damage induced by CORT and MPP+ was demonstrated. Thus, IGF-II is a potential therapeutic tool for prevention and treatment of PD patients suffering mild to moderate emotional stress.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Changes in macrofauna bioturbation during repeated heatwaves mediate changes in biogeochemical cycling of nutrients

The increasing frequency and intensity of marine heatwaves (MHWs) observed worldwide entails changes in the structure and functioning of ecological communities. While severe and extreme heatwaves often have more destructive effects, the more subtle effects of moderate and strong heatwaves may nevertheless affect ecosystem functioning through complex, context-dependent linkages between different processes. Here we conducted a laboratory experiment to study the effects of repeated short-term, strong MHWs on macrofauna bioturbation and associated solute fluxes as a measure of ecosystem functioning using natural soft-sediment communities from the Baltic Sea. Our results showed changes in both bioturbation and biogeochemical cycling of nutrients following short-term, strong heatwaves, which seemed to contribute to an enhanced degradation of organic matter in the seafloor and an enhanced exchange of solutes across the sediment-water interface as well as increased sediment oxygen consumption. Following changes in these processes, the relative contribution of macrofauna and the environmental context to ecosystem functioning was altered. Our results highlight the potential of even shorter-term, strong MHWs of having system-wide impacts due to changes in the mechanistic process of bioturbation underpinning the biogeochemical cycling of nutrients. This study also highlights the need to measure a wide range of variables for a comprehensive understanding of the changes in functioning under disturbances, such as MHWs

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.</p> <p>Methods</p> <p>NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.</p> <p>Results</p> <p>We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.</p> <p>Conclusion</p> <p>Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.</p

Calidad de las elecciones a titular del Ejecutivo en el Centro y Centro-occidente de México

Este libro, que tiene por objetivo analizar la calidad de las elecciones celebradas entre 2006 y 2011 para ocupar la titularidad del Poder Ejecutivo de las 14 entidades federativas de la República Mexicana que conforman las regiones Centro y Centro-occidente de este país, ha sido elaborado por investigadores pertenecientes a la Red Nacional de Investigación sobre la Calidad de la Democracia en México (Renicadem), la cual cuenta con un equipo de investigación en cada una de las entidades federativas del país. A su vez, esta Red constituye una de las cuatro líneas temáticas que componen la red temática del Conacyt “Sociedad civil y calidad de la democracia”. Con todo, la presente obra puede considerarse, en dos sentidos, como el resultado parcial de estudios realizados por investigadores que conforman la mencionada Renicadem. Por un lado, trata sólo de una de las varias dimensiones que esta Red ha establecido como necesarias para analizar la calidad de la democracia: la calidad electoral (otras dimensiones, que se encuentran en proceso de investigación, son calidad de vida, rendición de cuentas y Estado de derecho). También es parcial porque no abarca la totalidad de la República Mexicana, sino únicamente a las 14 entidades indicadas.UAE

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

Ciencias Sociales: Economía y Humanidades

Este volumen I contiene 29 capítulos arbitrados que se ocupan de estos asuntos en Tópicos Selectos de Ciencias Sociales: Economía y Humanidades, elegidos de entre las contribuciones, reunimos algunos investigadores y estudiantes.Gómez, presenta un breve examen de la producción y comercialización de rosa en México; Arpi y Portillo realiza un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; Bravo realiza un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; Caamal, Pat, Jerónimo y Romero realizan un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; Macías y Perales nos hablarán sobre una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; Figueroa, Pérez y Godínez se expresan acerca de la importancia de la comercialización del café en México; Sepúlveda, Sepúlveda y Pérez realizan un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; Duana mediante su trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; Figueroa, Pérez y Ramírez hacen un estudio acerca sobre la importancia de la Banca en México; Pérez, Figueroa, Godínez y Pérez presenta un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; Rodríguez, Espinosa y Márquez analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; Garza nos habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; Arroyo, Aguilar, Santoyo y Muñoz realizan un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; Pérez, Morett y Tecpan realizan un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; Godínez, Figueroa y Pérez realizan un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; Tavera y Cobos nos hablan de la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; Piña y Pérez hablan acerca de la reestructuración del capitalismo y crisis política en México; Gonzáles, Rucoba y Ramírez realizan un estudio de la rentabilidad de la producción de miel en el municipio de León, Guanjuato; Ramírez, Gutiérrez y Figueroa realizan un estudio acerca de la economía del maíz en la región metropolitana, Chiapas, 2014; Bueno, Méndez y Cruz realizan un estudio y análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; Pat, Caamal, Jerónimo y Mendoza presentan un estudio acerca de los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz. Vizuet presenta un trabajo de la construcción polisémica e histórica del concepto de la pobreza; Navarrete, Ríos y Arévalo presentan un estudio acerca de la producción ejidal de tomate rojo (Lycopersicum esculentum) en el DR-017, y su huella hídrica; Pérez y Piña hablan acerca de la productividad e inversión extranjera: La industria de Alimentos; Pérez, Figueroa, Godínez y Gómez presentan el trabajo sobre el sector primario en México; Pérez, Figueroa, Godínez y Gómez presentan acerca de los subsidios al campo como instrumento de política económica en México; Venegas, Perales y Del Valle realizan un estudio de rentabilidad de biodigestores y motogeneradores para diferentes tamaños de granjas porcinas en Michoacán