Central mechanisms mediating the hypophagic effects of oleoylethanolamide and N-acylphosphatidylethanolamines: different lipid signals?

The spread of "obesity epidemic" and the poor efficacy of many anti-obesity therapies in the long-term highlight the need to develop novel efficacious therapy. This necessity stimulates a large research effort to find novel mechanisms controlling feeding and energy balance. Among these mechanisms a great deal of attention has been attracted by a family of phospholipid-derived signaling molecules that play an important role in the regulation of food-intake. They include N-acylethanolamines (NAEs) and N-acylphosphatidylethanolamines (NAPEs). NAPEs have been considered for a long time simply as phospholipid precursors of the lipid mediator NAEs, but increasing body of evidence suggest a role in many physiological processes including the regulation of feeding behavior. Several observations demonstrated that among NAEs, oleoylethanolamide (OEA) acts as a satiety signal, which is generated in the intestine, upon the ingestion of fat, and signals to the central nervous system. At this level different neuronal pathways, including oxytocinergic, noradrenergic, and histaminergic neurons, seem to mediate its hypophagic action. Similarly to NAEs, NAPE (with particular reference to the N16:0 species) levels were shown to be regulated by the fed state and this finding was initially interpreted as fluctuations of NAE precursors. However, the observation that exogenously administered NAPEs are able to inhibit food intake, not only in normal rats and mice but also in mice lacking the enzyme that converts NAPEs into NAEs, supported the hypothesis of a role of NAPE in the regulation of feeding behavior. Indirect observations suggest that the hypophagic action of NAPEs might involve central mechanisms, although the molecular target remains unknown. The present paper reviews the role that OEA and NAPEs play in the mechanisms that control food intake, further supporting this group of phospholipids as optimal candidate for the development of novel anti-obesity treatments

The Endocannabinoid-Like Derivative Oleoylethanolamide at the Gut–Brain Interface: A “Lipid Way” to Control Energy Intake and Body Weight

In the last three decades, we witnessed a concomitant major increase in lifespan and a worldwide increasing incidence of chronic diseases such as obesity and type 2 diabetes. Disruption of energy homeostasis and systemic inflammation appear as common traits of these epidemic human diseases. The conventional endocannabinoid (eCB) system encompasses two G-protein–coupled receptors (GPCRs), their endogenous ligands (anandamide and 2-AG), and the enzymes essential for eCB biosynthesis and hydrolytic inactivation. Nonetheless, the family of eCB-like derivatives is growing constantly including other N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs) that do not bind canonical CB receptors rather other orphan G-protein–coupled receptors or peroxisome proliferator-activated nuclear receptors (PPARs). Here, we focus on the recent knowledge gathered on one such PPAR endocannabinoid ligand, oleoylethanolamide (OEA), from the identification of its synthesis in the small intestine to its anorexiant function with particular emphasis on our discovery of the main brain neurotransmitters system involved in its satiating effects

Histamine and neuroinflammation: insights from murine experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a chronic inflammatory, neurodegenerative disease of the CNS whose pathogenesis remains largely unknown, and available therapies are rarely successful in reversing neurological deficits or stopping disease progression. Ongoing studies on MS and the widely used murine model of experimental autoimmune encephalomyelitis (EAE) are focused on the many components of this complex and heterogeneous neurodegenerative disease in the hope of providing a mechanism-based characterization of MS that will afford successful strategies to limit and repair the neuronal damage. Recently, histamine has been postulated to have a key regulatory role in EAE and MS pathogenesis. Histamine is a mediator of inflammation and immune responses, exerting its many actions through four G protein-coupled receptors (H1,2,3,4R) that signal through distinct intracellular pathways and have different therapeutic potentials as they vary in expression, isoform distribution, signaling properties, and function. Immune cells involved in MS/EAE, including dendritic cells (DCs) and T lymphocytes, express H1R, H2R and H4R, and histamine may have varying and counteracting effects on a particular cell type, depending on the receptor subtypes being activated. Here, we review evidence of the complex and controversial role of histamine in the pathogenesis of MS and EAE and evaluate the therapeutic potential of histaminergic ligands in the treatment of autoimmune diseases

Videojuegos retro: una propuesta motivadora para integrar diseño electrónico y programación

En este artículo se describe la introducción de una propuesta de trabajo innovadora para los alumnos de Ingeniería Técnica Industrial en Electrónicacon intensificación en Informática y Telemática, en la EUETIB (Escola Universitària d’Enginyeria Tècnica Industrial de Barcelona). La propuesta se realiza como síntesis final de la titulación a nivel de Trabajo Fin de Carrera, pero puede realizarse también como parte de alguna asignatura de la intensificación. Los alumnos fabrican su propio videojuego retro a partir de unas especificaciones iniciales y el uso de un microcontrolador programable. El trabajo incluye diseño de hardware electrónico, programación en lenguaje ensamblador de los videojuegos implementados, así como fabricación y test del prototipo. Así, los alumnos aplican diferentes competencias propias de la intensificación que están cursando e integrarlas en un producto final, cuya característica lúdica hace que sea un objetivo altamente motivador. El hecho de implementar un videojuego retro de características sencillas, pero totalmente jugable, permite que la dificultad del trabajo sea razonable para su realización en un curso académico. Además, posibilita que el alumno pueda diseñar el hardware del prototipo con un nivel de complejidad apropiado para sus conocimientos. Los resultados iniciales son satisfactorios y se plantean propuestas para extender la experiencia en próximos cursos.Peer Reviewe

Artificial Hybridization Between Different Polyploid Levels In Glandularia (Verbenaceae)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141699/1/ajb207490.pd

Design issues in Human-centered AI for Marginalized People

Designing for migrants and asylum seekers requires the involvement of the whole society to improve the integration of citizens coming from countries with different cultures, religions, and life patterns. The design and development of AI companions for a personalized access to services is the horizon chosen to support and improve the inclusion of migrants and refugees both for the effectiveness of the services provided by public administration and local organizations, and for the quality of life of migrants and refugees. AI-based services are at the heart of the Digital Companion for migrants and asylum seekers designed to support more effective communication between public administrations and migrants. The human-centered, iterative, participative and critical design approach proved to be valuable to address the heterogeneous needs of the end-users as well as of the local service providers. Concrete issues in defining, testing, and refining the AI are discussed in view of provoking an impact on the whole society and towards a scenario of full development and upscaling

Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?

Histamine axons originate from a single source, the tuberomamillary nucleus (TMN) of the posterior hypothalamus, to innervate almost all central nervous system (CNS) regions. This feature, a compact cell group with widely distributed fibers, resembles that of other amine systems, such as noradrenaline or serotonin, and is consistent with a function for histamine over a host of physiological processes, including the regulation of the sleep-wake cycle, appetite, endocrine homeostasis, body temperature, pain perception, learning, memory, and emotion. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulation. While the histamine system is generally regarded as one single functional unit that provides histamine throughout the brain, evidence is beginning to accumulate in favor of heterogeneity of histamine neurons. The aim of this review is to summarize experimental evidence demonstrating that histamine neurons are heterogeneous, organized into functionally distinct circuits, impinging on different brain regions, and displaying selective control mechanisms. This could imply independent functions of subsets of histamine neurons according to their respective origin and terminal projections

Late spontaneous resolution of a double anterior chamber post deep anterior lamellar keratoplasty

A 31-year-old healthy male underwent deep anterior lamellar keratoplasty with big-bubble technique for treatment of keratoconus in his right eye. One week after surgery, he presented with detachment of the endothelium-Descemet complex with formation of a double anterior chamber, despite the apparent absence of an intraoperative Descemet membrane rupture. A subsequent intervention with the intent to relocate the corneal graft button was not effective, because the detachment appeared again one day later. The authors hypothesized that, at the time of the stromal dissection with big bubble technique, a small amount of air penetrated into the anterior chamber, creating a false pathway through the trabecular meshwork. The aqueous humor then penetrated the graft flowing through the false pathway, causing the endothelium-Descemet detachment. The persistence of that pathway, even after the intervention of graft repositioning, caused the failure of the latter procedure and persistence of the double chamber. We decided to wait and observe. The double anterior chamber spontaneously resolved in approximately three months