Dopamine D4 receptor activation counteracts nigrostriatal pathway activation by morphine: relevance in drug addiction.

Morphine induces dopamine release in the caudate putamen (CPu), which promotes stereotyped behavior and habit learning for drug-seeking and –taking. Nigrostriatal pathway stimulation by morphine is due to a removal of tonic inhibition arising from SNr GABA interneurons on SNc dopaminergic neurons through the mu opioid receptor (MOR). Long-term morphine exposure produces a series of adaptations in SNc dopamine neurons, which affect neuron excitability and dopamine output to CPu. We have previously shown that dopamine D4 receptor (D4R) stimulation counteracts acute and chronic morphine-induced accumulation of several transcription factors in the CPu (Gago et al., 2011 Brain Res.). Since D4R is expressed in the SNr (Rivera et al., Brain Res. 2003), we postulate that a functional D4R-MOR interaction at the midbrain level could exists. We have investigated the role of D4R in the morphine-induced nigroestriatal dopamine metabolism in the rat brain using biochemical and immunohistochemical techniques. We also have studied the influence of D4R on morphine-induced morphological changes in SNc dopamine neurons using both immunohistochemical and image analysis techniques. Finally, we examined a possible underlying mechanism of the D4R-MOR interaction at the SN level using in vitro quantitative receptor autoradiography. We have found that D4R activation restores dopamine metabolism in the nigroestriatal pathway after acute morphine treatment and prevents morphine-induced rise of tyroxine hydroxylase and dopamine transporter. Rats receiving a continuous treatment of morphine (6 days) showed SNc dopamine neurons with smaller size and higher circularity index compared with the controls animals. These morphine-induced morphological adaptatives changes were prevented when a D4R agonist (PD168,077) was administered at the same time with morphine. Autoradiographic studies demonstrated that the D4R agonist reduce the affinity of MOR. The present study provides evidence for the existence of a fully blocking effect of the D4R on the activation of dopaminergic nigroestriatal pathway by morphine.Financiación: P09-CVI- 4702 (Proyecto de Excelencia de la Junta de Andalucía

A Nexafs Study of Nitric Oxide Layers Adsorbed from a nitrite Solution onto a Pt(111) Surface

NO molecules adsorbed on a Pt(111) surface from dipping in an acidic nitrite solution are studied by near edge X-ray absorption fine structure spectroscopy (NEXAFS), X-ray photoelectron spectroscopy (XPS), low energy electron diffraction (LEED) and scanning tunnelling microscopy (STM) techniques. LEED patterns and STM images show that no long range ordered structures are formed after NO adsorption on a Pt(111) surface. Although the total NO coverage is very low, spectroscopic features in N K-edge and O K-edge absorption spectra have been singled out and related to the different species induced by this preparation method. From these measurements it is concluded that the NO molecule is adsorbed trough the N atom in an upright conformation. The maximum saturation coverage is about 0.3 monolayers, and although nitric oxide is the major component, nitrite and nitrogen species are slightly co-adsorbed on the surface. The results obtained from this study are compared with those previously reported in the literature for NO adsorbed on Pt(111) under UHV conditions

Gas-Phase Collision Induced Dissociation Mechanisms of Peptides : Theoretical and Experimental study of N-Formylalanylamide Fragmentation

International audienceIn order to shed light on the fragmentation mechanisms occurring during the collision induced dissociation (CID) of peptides in the gas phase, we have studied a model system, the N-formylalanylamide (HCO-Ala-NH2), by coupling experimental and theoretical methods. In particular, we have addressed two different questions arising in such experiments: (i) what is (are) the structure(s) of the ion before collision, and (ii) what are the fragmentation mechanisms occurring after collision with the target gas. For the first question, we coupled the potential energy surface (PES) study done by means of density functional theory (DFT), with Infra Red Multiple Photon Dissociation (IRMPD) spectroscopy. For the second problem, which is actually the main topic of the present work, we coupled quantum mechanics plus molecular mechanics (QM + MM) direct chemical dynamics simulations with tandem mass spectrometry (MS/MS). In addition, in order to better delineate the fragmentation mechanisms and validate those proposed by simulations, isotopic labeling experiments using 2H and 13C were performed. Thanks to the interplay between simulations and experiments, it was possible to successfully identify the fragmentation pathways leading to b1, y1, a1 and immonium ions. Our mechanisms support the "mobile proton" picture that is supposed to trigger the peptide fragmentation in the gas phase, confirming, from a chemical dynamics point of view, previous theoretical and experimental studies on similar systems

Patterson Function from Low-Energy Electron Diffraction Measured Intensities and Structural Discrimination

Surface Patterson Functions have been derived by direct inversion of experimental Low-Energy Electron Diffraction I-V spectra measured at multiple incident angles. The direct inversion is computationally simple and can be used to discriminate between different structural models. 1x1 YSi_2 epitaxial layers grown on Si(111) have been used to illustrate the analysis. We introduce a suitable R-factor for the Patterson Function to make the structural discrimination as objective as possible. From six competing models needed to complete the geometrical search, four could easily be discarded, achieving a very significant and useful reduction in the parameter space to be explored by standard dynamical LEED methods. The amount and quality of data needed for this analysis is discussed.Comment: 5 pages, 4 figure

3D Reconstruction of the Digestive System in Octopus vulgaris Cuvier, 1797 Embryos and Paralarvae during the First Month of Life

Octopus vulgaris aquaculture is limited due to poor biological knowledge of the paralarval stages (e.g., digestive system functionality), their nutritional requirements (e.g., adequate live diet) and standardization of rearing techniques. These factors are important in explaining the high mortality rate observed in this developmental stage under culture conditions. For a better understanding of nutrition biology of this species, we investigated the 3D microanatomy of the digestive tract of the embryo and paralarvae during the first month of life. O. vulgaris paralarvae digestive system is similar to that in the adult. The “descending branch” has a dorsal position and is formed by the buccal mass, oesophagus and crop. Ventrally, the “ascending branch” is formed by the intestine and the anus. The digestive gland, the posterior salivary glands and the inner yolk sac (in the case of the embryo and hatched paralarvae) are located between the “ascending” and “descending” branches. In the curve of the U-shaped digestive tract, a caecum and the stomach can be found. The reconstructions reveal that anatomically the digestive system is already complete when the paralarvae hatch. The reconstruction of the buccal mass at different post-hatching days has demonstrated that all the necessary structures for food intake are present. However, the radula surface in contact with the pharynx is very small on the first day of life. Although the digestive system has all the structures to feed, the digestive gland and radula take longer to reach full functionality. We have established four development periods: embryonic, early post-hatching, late post-hatching and juvenile-adult. The differentiation between these periods was done by type of feeding (endogenous or exogenous), the state of maturation and hence functionality of the digestive gland, type of growth (linear, no net, or exponential), and measurement of the arm lengths with respect to the mantle length. 3D reconstruction represents a new tool to study the morphology and functionality of the cephalopod digestive system during the first days of life

Propuestas para el posicionamiento del canal ECommerce en "La Ibérica" mediante estrategias digitales

Tenemos el orgullo de que en nuestro país tengamos varias marcas centenarias que aún siguen posicionándose en la mente del consumidor. Entre ellas, destacamos a La Ibérica, una empresa con 114 años, que desde la recolección del cacao en el Valle de la Convención en Cusco, obtención de materias primas, la producción de chocolates en su planta de Arequipa y la distribución a diferentes puntos de ventas; es una marca que ha ganado el cariño de su consumidor por generaciones, además de tener el reconocimiento de la calidad de sus productos. Un reto importante para la empresa es el llegar a esta nueva generación de clientes digitales, por lo que desde el 2021 cuenta con su propio Ecommerce en donde ofrecen toda la categoría de sus productos. Sin embargo, al pasar los años este canal se vuelve más retador ya que el usuario busca mayor información. En este trabajo de estudio, buscamos proponer diferentes estrategias digitales y una mejor experiencia de compra, que puedan implementarse en el Ecommerce de La Ibérica, con la finalidad de aumentar el alcance de su posicionamiento a un nuevo público más joven y digital que busca disfrutar de un auténtico chocolate para diferentes ocasiones de consumo.We are proud that in our country we have several century-old brands that still continue to position themselves in the consumer's mind. Among them, La Ibérica is a 114-year-old company, which from harvesting cocoa in the Convention Valley in Cusco, obtaining materials, producing chocolates in their plant in Arequipa and distributing to different points of sales; It is a brand that has won the affection of its consumers for generations, in addition to having recognition for the quality of its products. An important challenge for the company is to reach this new generation of digital customers, which is why since 2021 it has its own Ecommerce where they offer the entire category of their products. However, as the years go by, this channel becomes more challenging as the user seeks more information. In this study, we seek to propose different digital strategies and a better purchasing experience, which can be implemented in La Ibérica's Ecommerce, with the aim of increasing the reach of its positioning to a new, younger and digital audience that seeks to enjoy an authentic chocolate for different consumption occasions.Trabajo de Suficiencia Profesiona

Hierarchical regulation of sensor data transmission for networked telerobots

Networked telerobots carry sensors that send data, with stochastic transmission times, to a remote human operator, who must execute some real-time control task (e.g., navigation). In this paper we propose to regulate the sensory information being transmitted in order to guarantee soft real-time requirements and also optimize the quality of control, through a novel two-level hierarchical controller that both varies the amount of transmitted sensor data and dynamically reconfigures active sensors. Our controller has been implemented in a web-based teleoperator interface that is highly portable (it runs on desktop PCs, tablets, smartphones, etc.) and non-invasive, i.e., requires minimal modifications in the existing components of the system, thus being suitable for many applications. Here we present our regulation methods and the results of some experiments. They demonstrate the maximization of the transmitted data while guaranteeing the real-time requirements.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Graphene etching on SiC grains as a path to interstellar polycyclic aromatic hydrocarbons formation.

Polycyclic aromatic hydrocarbons as well as other organic molecules appear among the most abundant observed species in interstellar space and are key molecules to understanding the prebiotic roots of life. However, their existence and abundance in space remain a puzzle. Here we present a new top-down route to form polycyclic aromatic hydrocarbons in large quantities in space. We show that aromatic species can be efficiently formed on the graphitized surface of the abundant silicon carbide stardust on exposure to atomic hydrogen under pressure and temperature conditions analogous to those of the interstellar medium. To this aim, we mimic the circumstellar environment using ultra-high vacuum chambers and investigate the SiC surface by in situ advanced characterization techniques combined with first-principles molecular dynamics calculations. These results suggest that top-down routes are crucial to astrochemistry to explain the abundance of organic species and to uncover the origin of unidentified infrared emission features from advanced observations. © 2014 Macmillan Publishers Limited. All rights reserved