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espanol«Un paysage sans eau est comme un paysage mort, il lui manque une âme» nos dice Henri de Regnier en «Jours de pluie». Esta reflexion representa una constante en Regnier y, en esta linea, su obra esta jalonada de las ciudades que le marcaron en su vida cotidiana. Desde Honfleur, su ciudad natal, hasta Venecia, su ciudad de predileccion, pasando por sus lugares mas apreciados: Versalles, Paris…Ahora bien, el agua no es en Regnier un mero decorado. Su obra literaria esta impregnada de elementos acuaticos: rios, canales, fuentes, seres mitologicos… a los que dota de un significado personal, que nos permite hablar en este autor de una «Poetica del agua». En el presente estudio, repasaremos los lugares acuaticos de Regnier y sus simbolos hidricos mas apreciados para mostrar hasta que punto el motivo del agua es un hilo conductor altamente significativo en Henri de Regnier. EnglishIn «Jours de pluie», Henri de Regnier declares «Un paysage sans eau est comme un paysage mort, il lui manque une âme». This reflexion represents a constant in Regnier, and, in this line, his work is marked by the cities which left a mark on his daily life. From Honfleur, his hometown, to Venice, his city of predilection, through his most appreciated places: Versailles, Paris… However, water is not in Regnier a mere scenery; his literary work is covered with aquatic elements: rivers, canals, fountains, mythological creatures… to which he confers a personal meaning, which allows us to refer to a «poetics of water» in this author's work. In the present study, we will revise Regnier’s aquatic places and his most appreciated water symbols, to show the extent to which the water motif is an extremely significant guiding thread in Henri de Regnier.

Henri de Régnier, man of the north, apparently cold and distant, he discovers, mesmerised, the beauty and exoticism of the Mediterranean scenery in 1904, on board of the luxurious ya- cht “Le Velléda”. The impact this trip caused in the author was long-lasting, so much so that in 1906, he embarks again on another Medite- rranean cruise, this time on board of the yacht “Nirvana”, repeating almost the first itinerary port by port. During these journeys, Régnier takes careful note of his impressions on some travel notebooks. These notes will be used later by him to publish several works. Although Régnier was fascinated by the Medi- terranean, it was Venice –the city he discovers in 1899– the place which awakened in him an intoxicating passion. From that moment on, the life and the work of Régnier reveal the perfume of Venice. Space of ambiguity, of Canals, of re- flections and of masks, it is the ideal framework for the meeting with the otherness. Henri de Régnier, homme du nord, froid et distant en apparence, découvre émerveillé la beauté et l’exotisme du paysage méditerranéen en 1904, à bord du yacht Le Velléda. L’impact de ce voyage fut de si longue durée qu’Henri de Régnier décida de s’embarquer une nouve- lle fois en 1906 dans le yacht Nirvana. Cette nouvelle croisière reproduit à peu près le même itinéraire que le premier voyage. Au cours de ces traversées, Régnier note soigneusement ses impressions de voyage sur un carnet. Ces no- tes seront la base de plusieurs publications de l’auteur. Même si la mer Méditerranée fascina Henri de Régnier, ce fut Venise –ville que l’auteur découvre en 1899– qui éveilla une passion en- voûtante chez Régnier. À partir de cette décou- verte, la vie et l’œuvre d’Henri de Régnier dis- tillent le parfum de Venise. Espace d’ambiguïté, de canaux, de reflets et de masques, Venise est le cadre idéal pour la rencontre avec l’altérité.

This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grants SAF2010-16044 and SAF2013-46663-R (to V.A.), SAF2011-30312 and SAF2014-58286-C2-1-R (to L.H.-M.), SAF2011-30088 (to E.D.), and SAF2014-52413-R (to C.L.-O.) and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III Grants RD12/0042/0028 (to V.A.), RD12/0042/0011 (to J.T.), and RD12/0042/0002 (to L.H.-M.), with cofunding from the Fondo Europeo de Desarrollo Regional and the Progeria Research Foundation. J.A.G. is the recipient of a U-Mobility Grant from the Marie Curie cofunding of Regional, National and International Programme (Grant 246550). The Instituto Universitario de Oncología is supported by Obra Social Cajastur. The CNIC is supported by the MINECO and the Pro CNIC Foundation, and it is a Severo Ochoa Center of Excellence (MINECO Award SEV-2015-0505)., Rivera-Torres, J., Calvo, C.J., Llach, A., Guzmán-Martínez, G., Caballero, R., González-Gómez, C., Jiménez-Borreguero, L.J., Guadix, J.A., Osorio, F.G., López-Otín, C., Herraiz-Martínez, A., Cabello, N., Vallmitjana, A., Benítez, R., Gordon, L.B., Jalife, J., Pérez-Pomares, J.M., Tamargo, J., Delpón, E., Hove-Madsen, L., Filgueiras-Rama, D., Andrés, V.

© 2015, Springer-Verlag Berlin Heidelberg. Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p

Receptors for neurotransmitters require scaffolding proteins for membrane microdomain targeting and for regulating receptor function. Using a yeast two-hybrid screen, alpha-actinin-1, a major F-actin cross-linking protein, was identified as a binding partner for the C-terminal domain of metabotropic glutamate receptor type 5b (mGlu(5b) receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu(5b) receptor and alpha-actinin-1 in both transfected HEK-293 cells and rat striatum. The interaction of alpha-actinin-1 with mGlu(5b) receptor modulated the cell surface expression of the receptor. This was dependent on the binding of alpha-actinin-1 to the actin cytoskeleton. In addition, the alpha-actinin-1/mGlu(5b) receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning.

Most cellular functions are mediated by multiprotein complexes. In neurons, these complexes are directly involved in the proper neuronal transmission, which is responsible for phenomena like learning, memory, and development. In recent years studies based on two-hybrid screens and proteomic, biochemical, and cell biology approaches have shown that intracellular domains of G protein-coupled receptors (GPCRs) or heptaspanning membrane receptors (HSMRs) interact with intracellular proteins. These interactions are the basis of a protein network associated with these receptors, which includes scaffolding proteins containing one or several PDZ (post-synaptic-density-95/discs-large/zona occludens-1) domains, signaling proteins, and proteins of the cytoskeleton. The present article is focused on the emerging evidence for interactions of adenosine, dopamine, and metabotropic glutamate receptors, with scaffolding and cytoskeletal proteins that play a role in the targeting and anchoring of these receptors to the plasma membrane, thus contributing to neuronal development and plasticity. Finally, given the complexity of neurological disorders such as ischemic stroke, Alzheimer’s disease, and epilepsy, exploitation of these HSMR-associated interactions might prove to be efficient in the treatment of such disorders.

The results presented in this paper show that adenosine A2A receptor (A2AR) form homodimers and that homodimers but not monomers are the functional species at the cell surface. Fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) techniques have been used to demonstrate in transfected HEK293 cells homodimerization of A2AR, which are heptaspanning membrane receptors with enriched expression in striatum. The existence of homodimers at the cell surface was demonstrated by time-resolved FRET. Although agonist activation of the receptor leads to the formation of receptor clusters, it did not affect the degree of A2AR–A2AR dimerization. Both monomers and dimers were detected by immunoblotting in cell extracts. However, cell surface biotinylation of proteins has made evident that more than 90% of the cell surface receptor is in its dimeric form. Thus, it seems that homodimers are the functional form of the receptor present on the plasma membrane. A deletion mutant version of the A2A receptor, lacking its C-terminal domain, was also able to form both monomeric and dimeric species when cell extracts from transfected cells were analyzed by immunoblotting. This suggests that the C-terminal tail does not participate in the dimerization. This is relevant as the C-terminal tail of A2AR is involved in heteromers formed by A2AR and dopamine D2 receptors. BRET ratios corresponding to A2AR–A2AR homodimers were higher than those encountered for heterodimers formed by A2AR and dopamine D2 receptors. As A2AR and dopamine D2 receptors do indeed interact, these results indicate that A2AR homodimers are the functional species at the cell surface and that they coexist with A2AR/D2 receptor heterodimers.

The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL) cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 μg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30±0.04 to 0.17±0.02 (p, This work was supported by grants from the Spanish Ministry of Science and Innovation: SAF2011-30312 and CNIC2009-08 to Leif Hove Madsen, DPI2009-06999 to Rau´ l Benı´tez and from the Spanish Ministry of Health and Consume: FIS PI11/00747 to Vicenta Llorente. Funding from Redes de Investigacio´n Cooperativa, Instituto de Salud Carlos III, red REDINSCOR RD06-0003-0000 and RD06-0003-0015 is also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

G protein-coupled receptors are known to form homo- and heteromers at the plasma membrane, but the stoichiometry of these receptor oligomers are relatively unknown. Here, by using bimolecular fluorescence complementation, we visualized for the first time the occurrence of heterodimers of metabotropic glutamate mGlu(5) receptors (mGlu(5)R) and dopamine D(2) receptors (D(2)R) in living cells. Furthermore, the combination of bimolecular fluorescence complementation and bioluminescence resonance energy transfer techniques, as well as the sequential resonance energy transfer technique, allowed us to detect the occurrence receptor oligomers containing more than two protomers, mGlu(5)R, D(2)R and adenosine A(2A) receptor (A(2A)R). Interestingly, by using high-resolution immunoelectron microscopy we could confirm that the three receptors co-distribute within the extrasynaptic plasma membrane of the same dendritic spines of asymmetrical, putative glutamatergic, striatal synapses. Also, co-immunoprecipitation experiments in native tissue demonstrated the existence of an association of mGlu(5)R, D(2)R and A(2A)R in rat striatum homogenates. Overall, these results provide new insights into the molecular composition of G protein-coupled receptor oligomers in general and the mGlu(5)R/D(2)R/A(2A)R oligomer in particular, a receptor oligomer that might constitute an important target for the treatment of some neuropsychiatric disorders.

La littérature médiévale présente pas mal d'exemples de description de villes, aussi bien de villes "réelles" qu'imaginaires. Ces descriptions suivent des règles qui appartiennent à la descriptio civitatis et qui confèrent aux espaces des caractéristiques stables, que nous allons voir dans les textes. À côté de ces images, que nous pouvons appeler "prototypiques", nous trouvons des éléments qui servent à individualiser et qui font de chaque ville un espace différent. Dans cette étude, nous allons nous concentrer sur Yonec; nous allons voir de quelle manière la description offerte par Marie de France n'échappe pas aux conventions établies par la descriptio civitatis; cependant, les traits particularisants qu'elle y introduit donnent à la ville décrite une atmosphère de mystère et de merveille qui fait d'elle un espace situé dans l'Autre Monde des celtes, avec un caractère symbolique assez marqué. La literatura medieval presenta abundantes ejemplos de descripción de ciudades, tanto "reales" como imaginarias. Estas descripciones siguen las reglas fijadas por la descriptio civitatis, que otorgan a los espacios unas características estables que se manifiestan en los textos. Al margen de estas imágenes, que podemos llamar "prototípicas", encontramos elementos que sirven de individualizadores y que confieren a cada ciudad descrita un carácter único. En este estudio, vamos a fijar nuestra mirada en el relato Yonec, veremos como la descripción de Marie de France no escapa a las pautas que marca la descriptio civitatis pero, los rasgos particulares que ésta introduce, confieren a la ciudad descrita un halo de misterio y de "merveille" que la convierte en un espacio situado en el Otro Mundo celta, con un marcado carácter simbólico.