Intracrine prostaglandin E2 pro-tumoral actions in prostate epithelial cells originate from non-canonical pathways

Prostaglandin E2 (PGE2) increases cell proliferation and stimulates migratory and angiogenic abilities in prostate cancer cells. However, the effects of PGE2 on nontransformed prostate epithelial cells are unknown, despite the fact that PGE2 overproduction has been found in benign hyperplastic prostates. In the present work we studied the effects of PGE2 in immortalized, non-malignant prostate epithelial RWPE-1 cells and found that PGE2 increased cell proliferation, cell migration, and production of vascular endothelial growth factor-A, and activated in vitro angiogenesis. These actions involved a non-canonic intracrine mechanism in which the actual effector was intracellular PGE2 (iPGE2) instead of extracellular PGE2: inhibition of the prostaglandin uptake transporter (PGT) or antagonism of EP receptors prevented the effects of PGE2, which indicated that PGE2 activity depended on its carrier-mediated translocation from the outside to the inside of cells and that EP receptors located intracellularly (iEP) mediated the effects of PGE2. iPGE2 acted through transactivation of epidermal growth factor-receptor (EGFR) by iEP, leading to increased expression and activity of hypoxia-inducible factor-1? (HIF-1?). Interestingly, iPGE2 also mediates the effects of PGE2 on prostate cancer PC3 cells through the axis iPGE2-iEP receptors- EGFR-HIF-1?. Thus, this axis might be responsible for the growth-stimulating effects of PGE2 on prostate epithelial cells, thereby contributing to prostate proliferative diseases associated with chronic inflammation. Since this PGT-dependent non-canonic intracrine mechanism of PGE2 action operates in both benign and malignant prostate epithelial cells, PGT inhibitors should be tested as a novel therapeutic modality to treat prostate proliferative disease.Ministerio de Ciencia e Innovació

Intracrine prostaglandin E2pro-tumoral actions in prostateepithelial cells originate from non-canonical pathways

Prostaglandin E2(PGE2) increases cell proliferation and stimulates migratory andangiogenic abilities in prostate cancer cells. However, the effects of PGE2on non-transformed prostate epithelial cells are unknown, despite the fact that PGE2overproduction has been found in benign hyperplastic prostates. In the present workwe studied the effects of PGE2in immortalized, non-malignant prostate epithelialRWPE-1 cells and found that PGE2increased cell proliferation, cell migration, andproductionofvascularendothelialgrowthfactor-A,andactivatedinvitroangiogenesis.These actions involved a non-canonic intracrine mechanism in which the actualeffector was intracellular PGE2(iPGE2) instead of extracellular PGE2: inhibition of theprostaglandin uptake transporter (PGT) or antagonism of EP receptors prevented theeffects of PGE2, which indicated that PGE2activity depended on its carrier-mediatedtranslocation from the outside to the inside of cells and that EP receptors locatedintracellularly (iEP) mediated the effects of PGE2. iPGE2acted through transactivationof epidermal growth factor-receptor (EGFR) by iEP, leading to increased expressionand activityofhypoxia-induciblefactor-1α(HIF-1α).Interestingly,iPGE2alsomediatesthe effects of PGE2on prostate cancer PC3 cells through the axis iPGE2-iEP receptors-EGFR-HIF-1α. Thus, this axis might be responsible for the growth-stimulating effectsof PGE2on prostate epithelial cells, thereby contributing to prostate proliferativediseasesassociatedwithchronicinflammation.SincethisPGT-dependentnon-canonicintracrine mechanism of PGE2action operates in both benign and malignant prostateepithelial cells, PGT inhibitors should be tested as a novel therapeutic modality to treatprostate proliferative diseaseThis work was supported by grants SAF2011-26838 from the SpanishMinisterio de Ciencia e Innovació

LEGO© Mindstorms NXT and Q-Learning: a teaching approach for robotics in engineering

Robotics has become a common subject in many engineering degrees and postgraduate programs. Although at undergraduate levels the students are introduced to basic theoretical concepts and tools, at postgraduate courses more complex topics have to be covered. One of those advanced subjects is Cognitive Robotics, which covers aspects like automatic symbolic reasoning, decision-making, task planning or machine learning. In particular, Reinforcement Learning (RL) is a machine learning and decision-making methodology that does not require a model of the environment where the robot operates, overcoming this limitation by making observations. In order to get the greatest educational benefit, RL theory should be complemented with some hands-on RL task that uses a real robot, so students get a complete vision of the learning problem, as well as of the issues that arise when dealing with a physical robotic platform. There are several RL techniques that can be studied in such a subject; we have chosen Q-learning, since is a simple, effective and well-known RL algorithm. In this paper we present a minimalist implementation of the Q-learning method for a Lego Mindstorms NXT mobile robot, focused on simplicity and applicability, and flexible enough to be adapted to several tasks. Starting from a simple wandering problem, we first design an off-line model of the learning process in which the Q-learning parameters are studied. After that, we implement the algorithm on the robot, gradually enlarging the number of states-actions of the problem. The final result of this work is a teaching framework for developing practical activities regarding Q-learning in our Robotics subjects, which will improve our teaching.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

PROSTAGLANDIN E2 stimulates cancer-related phenotypes in prostate cancer PC3 cells through cyclooxygenase-2

Cyclooxygenase (COX)?derived prostaglandin E2 (PGE2) affects many mechanisms that have been shown to play roles in carcinogenesis. Recently, we found that, in androgenindependent prostate cancer PC3 cells, PGE2 acts through an intracrine mechanism by which its uptake by the prostaglandin transporter (PGT) results in increased intracellular PGE2 (iPGE2), leading to enhanced cell proliferation, migration, invasion, angiogenesis, and loss of cell adhesion to collagen I. These iPGE2?mediated effects were dependent on hypoxia?inducible factor 1?? (HIF?1?), whose expression increased upon epidermal growth factor receptor (EGFR) transactivation by a subset of intracellular PGE2 receptors. Here, we aimed to study the role of COX in PGE2 protumoral effects in PC3 cells and found that the effects were prevented by inhibition of COX?2, which highlights its crucial role amplifying the levels of iPGE2. Treatment with exogenous PGE2 determined a transcriptional increase in COX?2 expression, which was abolished by genetic or pharmacologic inhibition of PGT. PGE2?induced increase in COX?2 expression and, thereby, in transcriptional increase in HIF?1? expression was due to EGFR activation, leading to the activation of Phosphoinositide 3-kinase/Akt, Extracellular signal -regulated kinases 1/2, p38 and Mitogen- and stress-activated protein kinase-1 (PI3K/Akt, Erk1/2, p38 and MSK?1). Collectively, the data suggest that EGFR?dependent COX?2 upregulation by a novel positive feedback loop triggered by iPGE2 underlies the intracrine pro?tumoral effects of PGE2 in PC3 cells. Therefore, this feedback loop may be relevant in prostate cancer for the maintenance of PGE2?dependent cancer cell growth through amplifying the activity of the COX?2 pathway.Ministerio de Ciencia e Innovació

Red nucleus and rubrospinal tract disorganization in the absence of Pou4f1

The red nucleus (RN) is a neuronal population that plays an important role in forelimb motor control and locomotion. Histologically it is subdivided into two subpopulations, the parvocellular RN (pRN) located in the diencephalon and the magnocellular RN (mRN) in the mesencephalon. The RN integrates signals from motor cortex and cerebellum and projects to spinal cord interneurons and motor neurons through the rubrospinal tract (RST). Pou4f1 is a transcription factor highly expressed in this nucleus that has been related to its specification. Here we profoundly analyzed consequences of Pou4f1 loss-of-function in development, maturation and axonal projection of the RN. Surprisingly, RN neurons are specified and maintained in the mutant, no cell death was detected. Nevertheless, the nucleus appeared disorganized with a strong delay in radial migration and with a wider neuronal distribution; the neurons did not form a compacted population as they do in controls, Robo1 and Slit2 were miss-expressed. Cplx1 and Npas1, expressed in the RN, are transcription factors involved in neurotransmitter release, neuronal maturation and motor function processes among others. In our mutant mice, both transcription factors are lost, suggesting an abnormal maturation of the RN. The resulting altered nucleus occupied a wider territory. Finally, we examined RST development and found that the RN neurons were able to project to the spinal cord but their axons appeared defasciculated. These data suggest that Pou4f1 is necessary for the maturation of RN neurons but not for their specification and maintenance.Peer reviewedPeer Reviewe

Propuesta de plan de rehabilitación de la parroquia Santo Domingo de Guzmán, de la ciudad de Managua, Nicaragua.

Presenta una propuesta de plan de rehabilitación de la parroquia Santo Domingo de Guzmán, de la ciudad de Managua, Nicaragua. En el proceso de trabajo se tomaron varios aspectos como lo cultural, lo histórico, lo arquitectónico, lo patrimonial, lo estructural y sin faltar lo religioso por ser una edificación como su nombre lo dice es la casa del patrón de los Managua

Implicación de PGE2 intracelular en cáncer de próstata

El cáncer de próstata es la segunda causa de muerte por cáncer en varones y hasta la fecha, no existe ningún tratamiento eficaz en los estadios más avanzados de la enfermedad, haciendo necesaria la búsqueda de nuevas estrategias de tratamiento. En el presente trabajo se analiza la acción de la PGE2 en el desarrollo del cáncer de próstata. Estudios previos de nuestro grupo de investigación han demostrado que la PGE2 intracelular induce el aumento de la expresión de VEGF a través del factor inducible por hipoxia o HIF-1α en células HK-2, estos dos factores tienen una gran importancia en desarrollo tumoral, por ello nos propusimos analizar las acciones de la PGE2 en cáncer de próstata. Los resultados indican que la PGE2 intracelular induce la proliferación y migración de las células PC3, la expresión del factor inducible por hipoxia o HIF-1α y del principal factor proangiogénico VEGF, promoviendo la superviviencia celular y la angiogénesis, por este motivo proponemos una nueva terapia basada en inhibir el acceso de PGE2 al interior celular, lo que supondría eliminar únicamente la actividad tumorigénica de PGE2, preservando sus efectos fisiológico

Implicación de PGE2 intracelular en cáncer de próstata

El cáncer de próstata es la segunda causa de muerte por cáncer en varones y hasta la fecha, no existe ningún tratamiento eficaz en los estadios más avanzados de la enfermedad, haciendo necesaria la búsqueda de nuevas estrategias de tratamiento. En el presente trabajo se analiza la acción de la PGE2 en el desarrollo del cáncer de próstata. Estudios previos de nuestro grupo de investigación han demostrado que la PGE2 intracelular induce el aumento de la expresión de VEGF a través del factor inducible por hipoxia o HIF-1α en células HK-2, estos dos factores tienen una gran importancia en desarrollo tumoral, por ello nos propusimos analizar las acciones de la PGE2 en cáncer de próstata. Los resultados indican que la PGE2 intracelular induce la proliferación y migración de las células PC3, la expresión del factor inducible por hipoxia o HIF-1α y del principal factor proangiogénico VEGF, promoviendo la superviviencia celular y la angiogénesis, por este motivo proponemos una nueva terapia basada en inhibir el acceso de PGE2 al interior celular, lo que supondría eliminar únicamente la actividad tumorigénica de PGE2, preservando sus efectos fisiológico

Spatial Gradients of Intensity and Persistence of Soil Water Repellency Under Different Forest Types in Central Mexico

Organic residues release hydrophobic compounds to the soil that may induce soil water repellency (WR), which may inhibit infiltration andincrease runoff and soil loss rates. Although there are many studies on soil WR through the world, very few investigations have been con-ducted in Mexican areas. This paper studies the natural background of soil WR in soils from central Mexico under representative forest types,analyzing the spatial distribution of soil WR in relation with tree canopy, vegetation cover and main soil chemical (pH, CaCO3, organic Ccontent and exchangeable cations) and physical properties (texture). The water drop penetration time and the ethanol tests were used to assesspersistence and intensity of soil WR, respectively. Although soil WR was not related with soil properties, it decreased strongly from soil be-low the canopy of conifers to soil below oaks. When different types of vegetation cover were considered, the proportion of water-repellentsoil increased following the sequence: bare soil < shrubs and herbaceous plants < shrubs < trees from fir, fir-pine-oak and pine-oak forest.We found an inverse relation with distance to the tree trunks, contributing to create a patchy pattern of soil WR, with soils under the canopyof conifers showing the most severe WR levels. The spatial distribution of soil WR is also conditioned by microclimatic gradients, as per-sistence and intensity of soil WR were usually lower in shaded areas (upslope transects from the tree trunks), where soil moisture contentis expected to be higher on average through the year. Copyright © 2016 John Wiley & Sons, LtdMinisterio de Economía y Competitividad CGL2013-47862-C2-1-RMinisterio de Economía y Competitividad CGL 2012-38655-C04-0