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

A Hitchiker 's guide to digital social innovation

Social innovation plays an important role in addressing societal challenges. We map Digital Social Innovation (DSI) in terms of the international research efforts and investments made in Europe over the last decade. DSI aims to promote innovation and social change based on the network effect: meaning internet connections, web collaborative tools, sharing of open data and a process of bottom-up peer-supported activities and applications). Examples are given on the novel use of information platforms, data from sensor networks and community use of mobile phones. The impact measurement of the DSI initiative at social, economic and environmental level is presented. Our data comes from the EU activities and R&D grants awarded up to 2014. We describe the concept, the context, and the type of investments made by the European Union in this field. The final part of the paper concerns DSI impact evaluation and proposes a methodological framework for assessing specific results in a qualitative and quantitative way

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

The mRNA expression of SETD2 in human breast cancer: Correlation with clinico-athological parameters

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer

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

Workplace Contextual Supports for LGBT Employees: A Review, Meta‐Analysis, and Agenda for future Research

The past decade has witnessed a rise in the visibility of the lesbian, gay, bisexual, and transgender (LGBT) community. This has resulted in some organizational researchers focusing their attention on workplace issues facing LGBT employees. While empirical research has been appropriately focused on examining the impact of workplace factors on the work lives of LGBT individuals, no research has examined these empirical relationships cumulatively. The purpose of this study was to conduct a comprehensive review and meta‐analysis of the outcomes associated with three workplace contextual supports (formal LGBT policies and practices, LGBT‐supportive climate, and supportive workplace relationships) and to compare the relative influence of these workplace supports on outcomes. Outcomes were grouped into four categories: (a) work attitudes, (b) psychological strain, (c) disclosure, and (d) perceived discrimination. Results show that supportive workplace relationships were more strongly related to work attitudes and strain, whereas LGBT supportive climate was more strongly related to disclosure and perceived discrimination compared to the other supports. Our findings also revealed a number of insights concerning the measurement, research design, and sample characteristics of the studies in the present review. Based on these results, we offer an agenda for future research

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

Artificial Hybridization Between Different Polyploid Levels In Glandularia (Verbenaceae)

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