Allosteric Modulators for GPCRs as a Therapeutic Alternative with High Potential in Drug Discovery

The superfamily of G protein-coupled receptors (GPCRs) consists of biological microprocessors that can activate multiple signaling pathways. Most GPCRs have an orthosteric pocket where the endogenous ligand(s) typically binds. Conversely, allosteric ligands bind to GPCRs at sites that are distinct from the orthosteric binding region and they modulate the response elicited by the endogenous ligand. Allosteric ligands can also switch the response of a GPCR after ligand binding to a unique signaling pathway, these ligands are termed biased allosteric modulators. Thus, the development of allosteric ligands opens new and multiple ways in which the signaling pathways of GPCRs can be manipulated for potential therapeutic benefit. Furthermore, the mechanisms by which allosteric ligands modulate the effects of endogenous ligands have provided new insights into the interactions between allosteric ligands and GPCRs. These new findings have a high potential to improve drug discovery and development and, therefore, creating the need for better screening methods for allosteric drugs to increase the chances of success in the development of allosteric modulators as lead clinical compounds

Implicaciones del filtrado de calidad del índice de vegetación EVI para el seguimiento funcional de ecosistemas

Revista oficial de la Asociación Española de Teledetección[EN] The use of MODIS (Moderate Resolution Imaging Spectroradiometer) images for ecosystem monitoring is currently widespread both in research and management. Vegetation indexes (VIs), such as NDVI (Normalized Difference Vegetation Index) and EVI (Enhanced Vegetation Index), are broadly extended for monitoring ecosystem functioning. These indexes are linear estimators of the fraction of photosynthetically active radiation intercepted by vegetation (fAPAR), the main control of net primary production. However, VIs are subject to errors. To handle such errors, the MOD13Q1 VI product includes a Quality Assessment (QA) layer with information about pixel quality. This QA layer represents a great advantage for final users, allowing filtering of pixels with VI values influenced by aerosols, clouds, snow, or shadows. However, the use of homogeneous filtering criteria throughout a heterogeneous region may cause the systematic loss of information in particular areas or times of the year. In this paper, we assessed the effect of different filtering criteria on spatiotemporal data of EVI for the period 2001-2010 in the Iberian Southeast. Our results showed no effect of filtering on EVI availability and magnitude values in low altitudes, but strong and significant differences in the mountains depending on the filter applied: aerosol, shadows or snow filters. Such effects of filtering on the EVI revealed that monitoring programs in these regions should include a filtering step before exploring for abrupt changes or longterm trends in the EVI time series.[ES] El seguimiento de los ecosistemas con imágenes procedentes del sensor MODIS (Moderate Resolution Imaging Spectroradiometer, espectroradiómetro de imágenes de resolución media) está actualmente muy extendido tanto en tareas de investigación como de gestión. Los índices de vegetación NDVI (Normalized Difference Vegetation Index, índice de vegetación de la diferencia normalizada) y EVI (Enhanced Vegetation Index, índice de vegetación mejorado) son ampliamente usados para la caracterización del funcionamiento ecosistémico. Ambos índices se emplean como estimadores lineales de la fracción de radiación fotosintéticamente activa interceptada por la vegetación (fAPAR), el principal control de la producción primaria. A pesar de sus ventajas, las imágenes de índices de vegetación no están libres de errores. El producto índices de vegetación MOD13Q1 proporciona una capa QA (Quality assessment, evaluación de la calidad) que informa sobre la calidad asociada a cada píxel. Esta información representa una gran ventaja para el usuario, al permitir filtrar aquellos datos que puedan inducir a errores al verse alterados por la presencia de aerosoles, nubes, nieve o sombras. Sin embargo, la realización de un filtrado homogéneo a lo largo de una gran región puede ocasionar la pérdida sistemática de información en determinadas zonas o épocas del año, introduciendo así un sesgo espacial o en la serie temporal. Esta situación puede ser especialmente crítica en regiones con alta heterogeneidad ambiental, como el Sureste Ibérico. En este trabajo evaluamos el efecto que el filtrado de calidad tiene sobre la información espacial y temporal de la base de datos del EVI en el periodo 2001-2010. Los resultados, expresados en porcentaje de información perdida (filtrada) y como efecto de estas pérdidas sobre los valores del EVI, indican que mientras que las áreas de menor altitud no se ven afectadas por el filtrado, las regiones de alta montaña muestran variaciones significativas en sus valores del EVI cuando son filtrados por aerosoles, sombras o la presencia de hielo o nieve. Esto pone de manifiesto la importancia del establecimiento de un protocolo para el procesamiento de la información que considere las características espaciales y temporales de los datos a filtrar.Este trabajo ha sido financiado por el Ministerio de Innovación y Ciencia (Proyecto CGL2010- 22314), la Junta de Andalucía (Proyecto SEGALERT, P09-RNM-5048) y el Centro Andaluz para la Evaluación y Seguimiento del Cambio Global (CAESCG) (Proyecto GLOCHARID).Reyes-Díez, A.; Alcaraz-Segura, D.; Cabello-Piñar, J. (2015). Implications of quality filtering of Enhanced Vegetation Index (EVI) for ecosystem functioning monitoring. Revista de Teledetección. (43):11-30. https://doi.org/10.4995/raet.2015.3316SWORD11304

MODELO DE UNA RED DE CONOCIMIENTO SOSTENIBLE PARA LOS TALLERES ARTESANALES DE PIEDRA DE DZITYÁ YUCATÁN

El sistema capitalista en el que se vive propicia diferentes problemáticas en los diversos sectores productivos. Estas problemáticas son la búsqueda de la maximización de la ganancia, como la confrontación, la destrucción del tejido social, la competencia exacerbada y la crisis ambiental; sobre todo en aquellas actividades que coexisten entre la tradición y la modernidad como es el caso de los talleres artesanales de piedra. Ante esta situación, se exploran racionalidades económicas diferentes que permitan hacer prácticas eficientes no desde la lógica de mercado sino desde una lógica solidaria con la humanidad, la naturaleza y la cultura, así como lo propone la “Economía Social y Solidaria” y “Redes de conocimiento”. Esta alternativa se plantea en respuesta a las tres problemáticas principales que se presentan en la actividad artesanal de piedra de Dzityá: 1) la pérdida del componente cultural al pasar de una producción artesanal hacia una destinada al sector de la construcción; 2) el impacto ambiental que generan en la extracción de la piedra como materia prima y su proceso de transformación y 3) la fuerte disociación que existe entre el grupo de artesanos de la misma comunidad. El presente trabajo muestra el bosquejo del modelo ideal para la construcción de una red de conocimiento sostenible y solidaria que propicie la búsqueda e implementación de proyectos que ayuden a resolver los problemas comunes de estos tallere

Pelvic floor dysfunction in Mexican women

Background: Pelvic floor dysfunction (PFD) is a term used to describe a variety of disorders that involve moderate to severe impairment of the pelvic floor muscles. Throughout their lives, up to 46% of women will present at least one form of PFD and may even have a combination of this pathology. These afflictions have a profound influence on women’s general well-being and quality of life, as well as being an immense economic burden for global health systems. Methods: This was a populational study which used surveys made in Google Forms of different questionnaires validated in Spanish [Urinary Incontinence Questionnaire (ICIQ), Female Sexual Function Index (IFSF), CPPQ Questionnaire for chronic pelvic pain, Wexner anal incontinence scale and quality of life] which were taken by women with access to social networks and who agreed to carry out an anonymous survey. Results: Seven hundred and twenty-one participants were evaluated, a total of 61.4% (443) responded positively to involuntary loss of urine, 35% had presented discomfort during sexual activity or lack of sexual interest, 14% had genital pain and 16% reported involuntary loss of feces or gas. Of all the patients that answered any of these questioners positively, only 33% had sought medical attention in the past. Conclusions: We concluded that in our population PFD is underdiagnosed. Our populations prevalence of urinary incontinence and pelvic pain is within the internationally described margins; anal incontinence is above international reports, and our population presented a lower prevalence of sexual dysfunction. With this new information we must impulse awareness to guide various preventive behaviors

Agro-industrial evaluation of new sugarcane (Saccaharum spp.) hybrids in the dry tropic under no watering conditions

Objetive: The objective of this research was to select new sugarcane hybrids with better adaptation and performance in the field and industrial within the supply area of ??the Quesería sugar mill of the Beta San Miguel group (BSM). Design/methodology/approach: A group of 11 new hybrids were established in the agroindustrial phase, in order to compare their adaptation and field and the industrial performance using the commercial hybrid Mex 69-290 as control. Results: The results obtained indicated that during the soca cycle and under local soil conditions, the hybrids ColMex 05-484, ColMex 05-38 (c9) and ColMex 05-627, demonstrated the highest estimated field yields, with values ??of 154, 149 and 143 t / ha-1 respectively. Regarding the highest values ??of percentage of sucrose in cane (Pol), at 12 months of age of the plant, it was obtained by the hybrids ColMex 05-147 (16.8%), ColMex 08-38 (C8) (16.5%) and ColMex 05-897 (16.1%), considered by its intermediate cycle maturation curve. Limitations on study/implications: The limitations that could affect the results of the investigation were; the abundance of stones on the topsoil and the poor distribution of rainfall during the development of the crop (1203 mm). Findings/conclusions: It can be concluded that after analyzing the agricultural and industrial performance that, the best hybrid was: ColMex 05-484, surpassing the commercial control Mex 69-290.Objective: To select new sugarcane (Saccaharum spp.) hybrids with better adaptability and higher field and industrial performance, within the supply area of the Quesería Sugar Mill of the Beta San Miguel group (BSM). Design/methodology/approach: We set up a group of 11 new hybrids in the agro-industrial phase in order to compare their adaptability and their field and industrial performance, using the Mex 69-290 commercial hybrid as control. Results: The obtained results indicated that during the soca cycle and under local soil conditions, the ColMex 05-484, ColMex 05-38 (C9), and ColMex 05-627 hybrids produced the highest estimated field yields, with values of 154, 149, and 143 t/ha-1, respectively. The highest percentages of sucrose in cane (Pol) in 12-month-old plants were observed in the ColMex 05-147 (16.8%), ColMex 08-38 (C8) (16.5%), and ColMex 05-897 (16.1%) hybrids, according to their intermediate stage maturity curve. Study limitations/implications: The limitations that could affect the results of the research were the abundance of stones on the topsoil and the poor distribution of rainfall during crop development (1,203 mm). Findings/conclusions: After analyzing the agricultural and industrial performance of several hybrids, we can conclude that ColMex 05-484 was the best, surpassing the Mex 69-290 commercial control

The force-velocity profile as determinant of spike and serve ball speed in top-level male volleyball players

Understanding the relationship between mechanical variables derived from actions such as jumping, sprinting, or ballistic bench press throwing and sport-specific performance moves is of scientific and practical interest for strength and conditioning coaches for improving training programs. We examined the association between mechanical variables derived from the force-velocity (FV) profiles of the aforementioned actions and spike and serve ball speeds in elite volleyball players. Twenty-two male elite volleyball players (age: 24.3 ± 4.5 years; height: 1.89 ± 0.06 m; body mass: 86.3 ± 8.6 kg) were tested in two sessions. Squatting, sprinting, and bench press throwing FV profiles were determined in the first session, while spike and serve ball speeds were assessed in the second session. The theoretical maximal force (F0) of vertical jumping, the theoretical maximal velocity of sprinting, and the F0 of bench press throwing in ascending order, were strongly associated (rs range 0.53– 0.84; p<0.05) with spike and serve ball speeds. These mechanical variables explained 20%- 36% of the variability in spike and serve ball speeds, with a greater influence on the serve speed. These results suggest that assessing jumping, sprinting, and bench press throwing force-velocity profiles might help provide player-specific training programs and optimize performance in these technical-tactical actions in male elite volleyball players

Sistema para el Seguimiento del funcionamiento de ecosistemas en la Red de Parques Nacionales de España mediante Teledetección

Revista oficial de la Asociación Española de Teledetección[EN] Management of protected areas in the current context of global change requires approaches to characterize and to monitor ecosystem functioning. Remote sensing provides adequate tools for that because it provides índices that inform repeatedly and for large areas of land, about matter and energy exchanges between the biota and land surface. Considering this principle, and the continuous improvements in the availability of satellite data of higher quality and friendly use, we have developed with the Autonomous Organization of National Parks of Spain (OAPN), a monitoring system that complements other monitoring initiatives from this agency to inform about the conservation status of national parks. The system, called REMOTE, is based on the most used spectral vegetation indices on scientific literature, EVI (Enhanced Vegetation Index) and NDVI (Normalized Difference Vegetation Index), derived from the time series of satellite images of the MODIS-Terra sensor. The systems allows to progress in identification of reference conditions to understand and predict ecosystems response against environmental perturbations or management actions, and their directional changes (trends) they are experiencing. Likewise, establishment of reference conditions helps to identify anomalies that warn of sudden changes in ecosystem functioning. The system uses as ecosystem functioning indicators three attributes related to the annual carbon gains (net primary production) by the canopy, their seasonality and phenology. In addittion, Remote has been designed and programmed on open and free software allowing future modifications and improvements in an easy way. The implementation of this system aims to inform decision-makers and managers of the Network of National Parks of Spain about the health and conservation status of ecosystems.[ES] La gestión de las áreas protegidas en el actual contexto de cambio global requiere de aproximaciones que permitan caracterizar y seguir el funcionamiento de los ecosistemas. La teledetección ofrece herramientas para ello, ya que proporciona índices que informan reiteradamente y para grandes porciones de territorio, de los intercambios de materia y energía que tienen lugar entre la biota y la superficie terrestre. Considerando este principio, y la cada vez mayor disponibilidad de información satelital de calidad y facilidad de uso, desarrollamos junto con el Organismo Autónomo de Parques Nacionales de España (OAPN), un sistema de seguimiento que complementa a otras iniciativas desarrolladas por este organismo para informar del estado de conservación de los parques nacionales. El sistema, denominado REMOTE, se basa en el empleo de los índices de vegetación espectrales (IVs) de uso más extendido (EVI -índice de vegetación mejorado- y NDVI -índice de vegetación normalizado-), derivados de la serie temporal de imágenes satelitales del sensor MODIS-Terra. El sistema permite avanzar en la identificación de las condiciones de referencia para la comprensión y predicción de las respuestas de los ecosistemas frente a perturbaciones e interven-ciones, y de los cambios direccionales que éstos están experimentando (tendencias). Así mismo ayuda a la detección de anomalías recientes que alertan de cambios bruscos en el funcionamiento de los ecosistemas. REMOTE se carac-teriza porque usa como indicadores tres atributos relacionados con las ganancias de carbono anuales (productividad primaria neta) por parte del dosel vegetal, su estacionalidad y fenología. Además, está diseñado y programado con software libre y gratuito, lo que permitirá modificar o implementar mejoras en él fácilmente. Su implementación tiene como objetivo informar a los tomadores de decisiones y gestores de la Red de Parques Nacionales de España de la salud y estado de conservación de los ecosistemas.Los trabajos han sido financiados por el Organismo Autónomo de Parques Nacionales (OAPN), y el Centro Andaluz para la Evaluación y Seguimiento del Cambio Global (CAESCG).Cabello, J.; Alcaraz-Segura, D.; Reyes, A.; Lourenço, P.; Requena, JM.; Bonache, J.; Castillo, P.... (2016). System for monitoring ecosystem functioning of Network of National Parks of Spain with remote sensing. Revista de Teledetección. (46):119-131. doi:10.4995/raet.2016.5731.SWORD1191314

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE