Interest of qualitative and quantitative profiling of endocannabinoids for evaluation of their implication in drug addiction process

Introduction: In the middle of the 90's, the discovery of endogenous ligands for cannabinoid receptors opened a new era in this research field. Amides and esters of arachidonic acid have been identified as these endogenous ligands. Arachidonoylethanolamide (anandamide or AEA) and 2-Arachidonoylglycerol (2-AG) seem to be the most important of these lipid messengers. In addition, virodhamine (VA), noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA) have been shown to bind to CB receptors with varying affinities. During recent years, it has become more evident that the EC system is part of fundamental regulatory mechanisms in many physiological processes such as stress and anxiety responses, depression, anorexia and bulimia, schizophrenia disorders, neuroprotection, Parkinson disease, anti-proliferative effects on cancer cells, drug addiction, and atherosclerosis. Aims: This work presents the problematic of EC analysis and the input of Information Dependant Acquisition based on hybrid triple quadrupole linear ion trap (QqQLIT) system for the profiling of these lipid mediators. Methods: The method was developed on a LC Ultimate 3000 series (Dionex, Sunnyvale, CA, USA) coupled to a QTrap 4000 system (Applied biosystems, Concord, ON, Canada). The ECs were separated on an XTerra C18 MS column (50 × 3.0 mm i.d., 3.5 μm) with a 5 min gradient elution. For confirmatory analysis, an information-dependant acquisition experiment was performed with selected reaction monitoring (SRM) as survey scan and enhanced produced ion (EPI) as dependant scan. Results: The assay was found to be linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2-AGE, and NADA and 1-20 ng/mL for 2-AG using 0.5 mL of plasma. Repeatability and intermediate precision were found less than 15% over the tested concentration ranges. Under non-pathophysiological conditions, only AEA and 2-AG were actually detected in plasma with concentration ranges going from 104 to 537 pg/mL and from 2160 to 3990 pg/mL respectively. We have particularly focused our scopes on the evaluation of EC level changes in biological matrices through drug addiction and atherosclerosis processes. We will present preliminary data obtained during pilot study after administration of cannabis on human patients. Conclusion: ECs have been shown to play a key role in regulation of many pathophysiological processes. Medical research in these different fields continues to growth in order to understand and to highlight the predominant role of EC in the CNS and peripheral tissues signalisation. The profiling of these lipids needs to develop rapid, highly sensitive and selective analytical methods.

Census 2011 Ireland and Northern Ireland: Key findings

Following publication of the individual Census 2011 results from the Republic of Ireland (ROI) and Northern Ireland (NI), the Central Statistics Office and Northern Ireland Statistics and Research Agency have teamed up to produce a comparative report, Census 2011 Ireland and Northern Ireland. The report presents comparative analysis in a��range of areas including demographics, households, place of birth, religion, health, housing and��travel. Some key findings relevant to ageing and older people across the island of Ireland are summarised in this document:��Census 2011 Ireland and Northern Ireland: Key findings

The Mental Health Bill 2006: Briefing sheets on key policy areas

Includes: supervised community treatment, professional roles, nearest relatives, definition of mental disorder, cirteria for detention, mental health review tribuneral, general information, implementing government policy, Bournewood safteguards

Health inequalities - Vulnerable groups - National key resources

Is part of Health inequalities - Vulnerable groups Has part Vulnerable adults (DH)

Health inequalities - Vulnerable groups - Regional key resources

Has part Understanding the health needs of migrants in the South East region Assault Prevention Data Sharing Toolkit

Smart Schools = Smart Economy

Ireland’s national recovery will be rooted in further developing our outstanding education system. Schools and colleges are key contributors to economic growth and national competitiveness, providing successive generations with the skills and abilities necessary for a vibrant economy and inclusive society. Within the educational system, teachers play a central role in developing the potential of our children and young people. Our education system must continue to be responsive to and supportive of the economic life of this country.

Supporting A Better Transition From Second Level To Higher Education: Key directions and Next Steps

Supporting A Better Transition From Second Level To Higher Education. Provided by the Department of Education and Skills, Ireland.

A key transcription cofactor on the nascent sex chromosomes of European tree frogs (Hyla arborea)

We show that MED15, a key component of the transcription complex Mediator, lies within the nonrecombining segment of nascent sex chromosomes in the male-heterogametic Hyla arborea. Both X and Y alleles are expressed during embryonic development and differ by three frame-preserving indels (eight amino acids in total) within their glutamine-rich central part. These changes have the potential to affect the conformation of the Mediator complex and to activate genes in a sex-specific way and might thus represent the first steps toward the acquisition of a male-specific function. Alternatively, they might result from an ancestral neutral polymorphism, with different alleles picked by chance on the X and Y chromosomes when MED15 was trapped in the nonrecombining segment.

Prevention of Venous Thromboembolism: A Key Patient Safety Priority

Prevention of venous thromboembolism (VTE) is an important part of our strategy to improve patient safety.The Northern Ireland HSC Safety Forum established and facilitated a regional collaborative which developed a single VTE Risk Assessment Tool for N.Ireland.

Patterns of recovery following focal hemispheric lesions : relationship between lasting deficit and damage to specialized networks

Rapport de synthèse : Objectif : Les déficits cognitifs présents dans la phase aiguë d'une lésion hémisphérique focale ont tendance à être de nature plus importante et plus générale que les déficits résiduels qui persistent dans la phase chronique de récupération. Nous avons investigué, dans le cadre de ce travail, les modèles de récupération auditive et la relation qui se dessine entre les déficits et les dommages relatifs à des réseaux spécifiques, pris comme modèle cognitif des fonctions auditives. De nombreuses études humaines dans les domaines de la neuropsychologie, de la psychophysique ainsi que des études d'activation suggèrent que les processus de reconnaissance et de localisation sonores sont effectués par l'intermédiaire de réseaux distincts tant sur le plan anatomique que fonctionnel : il s'agit des zones de traitement du «What» et du «Where », qui sont toutes deux présentes dans les deux hémisphères. Des études ont démontré que des lésions hémisphériques focales gauches ou droites, centrées sur ces réseaux, sont associées dans la phase chronique de récupération à des déficits correspondant en ce qui concerne la reconnaissance et/ou la localisation sonore. Méthode : Dans le cadre de ce travail, nous avons analysé les résultats concernant les performances auditives chez 24 patients ayant subi des lésions hémisphériques focales avec déficits secondaires dans des tâches de reconnaissance, de localisation et/ou de perception du mouvement sonore lors d'un premier testing effectué en phase aiguë (9 patients), en phase subaiguë (6 patients) ou en phase chronique précoce (9 patients). La totalité de ces patients ont bénéficié d'un second testing en phase chronique. Les observations effectuées ont servi à l'élaboration de patterns de récupération auditive. Résultats : Tous les 24 patients avaient initialement un déficit dans le domaine de la localisation et/ou de la perception du mouvement sonore. Dans la phase aiguë, ce déficit survenait sans atteinte spécifique du réseau «Where » chez presque la moitié des patients ; en revanche, cette situation n'était jamais observée chez les patients testés en phase chronique précoce. Une absence de récupération avait tendance à être associée à un dommage spécifique au réseau concerné ainsi qu'à la persistance d'un déficit au-delà de la phase aiguë. Les déficits résiduels n'étaient par ailleurs pas strictement en lien avec la taille lésionnelle ou l'étendue de l'atteinte du réseau spécifique. Conclusion : Nos résultats suggèrent que des mécanismes distincts sous-tendent la récupération et la plasticité à différentes périodes temporelles post-lésionnelles.

Characterization of the rice PHO1 gene family reveals a key role for OsPHO1;2 in phosphate homeostasis and the evolution of a distinct clade in dicotyledons.

Phosphate homeostasis was studied in a monocotyledonous model plant through the characterization of the PHO1 gene family in rice (Oryza sativa). Bioinformatics and phylogenetic analysis showed that the rice genome has three PHO1 homologs, which cluster with the Arabidopsis (Arabidopsis thaliana) AtPHO1 and AtPHO1;H1, the only two genes known to be involved in root-to-shoot transfer of phosphate. In contrast to the Arabidopsis PHO1 gene family, all three rice PHO1 genes have a cis-natural antisense transcript located at the 5 ' end of the genes. Strand-specific quantitative reverse transcription-PCR analyses revealed distinct patterns of expression for sense and antisense transcripts for all three genes, both at the level of tissue expression and in response to nutrient stress. The most abundantly expressed gene was OsPHO1;2 in the roots, for both sense and antisense transcripts. However, while the OsPHO1;2 sense transcript was relatively stable under various nutrient deficiencies, the antisense transcript was highly induced by inorganic phosphate (Pi) deficiency. Characterization of Ospho1;1 and Ospho1;2 insertion mutants revealed that only Ospho1;2 mutants had defects in Pi homeostasis, namely strong reduction in Pi transfer from root to shoot, which was accompanied by low-shoot and high-root Pi. Our data identify OsPHO1;2 as playing a key role in the transfer of Pi from roots to shoots in rice, and indicate that this gene could be regulated by its cis-natural antisense transcripts. Furthermore, phylogenetic analysis of PHO1 homologs in monocotyledons and dicotyledons revealed the emergence of a distinct clade of PHO1 genes in dicotyledons, which include members having roles other than long-distance Pi transport.

Integration in strategic alliances : a conceptual framework of IT use in marketing as NPD key factor

En una economia basada en el coneixement, la innovació del producte es considera un factor clau a l'hora de determinar la competitivitat, la productivitat i el creixement d'una companyia. No obstant això, l'experiència de les companyies demostra la necessitat d'un nou model de gestió de la innovació del producte: una gestió basada en el màrqueting, en què la cooperació i l'ús intensiu de les tecnologies de la informació i de la comunicació (TIC) són especialment importants. En els darrers anys, la bibliografia sobre màrqueting ha analitzat el paper de la cooperació en l'èxit del procés d'innovació. No obstant això, fins ara pocs treballs han estudiat el paper que té l'ús de les TIC en el màrqueting en l'èxit del desenvolupament de nous productes (NPD, New Product Development en anglès). És una omissió curiosa, tenint en compte que el nou entorn competitiu és definit per una economia i una societat basades principalment en l'ús intensiu de les TIC i del coneixement. L'objectiu d'aquest treball és investigar el paper que l'ús de les TIC en el màrqueting té en el procés de desenvolupament de nous productes, com a element que reforça la integració d'agents al projecte, afavorint l'establiment de relacions dirigides a la cooperació i l'adquisició d'intel·ligència de mercat útil en el procés de desenvolupament de nous productes. L'estudi d'una mostra de 2.038 companyies de tots els sectors de l'activitat econòmica a Catalunya ens permet contrastar hipòtesis inicials i establir un perfil de companyia innovadora basat en les importants relacions que hi ha entre la innovació, l'ús de TIC en el màrqueting i la integració. Sobresurten dues idees en la nostra anàlisi. En primer lloc, l'ús intensiu de les TIC en el màrqueting fa que la companyia sigui més innovadora, ja que percep que el seu ús ajuda a superar barreres a la innovació i accelera els processos, que es tornen més eficients. En segon lloc, incrementant l'ús de les TIC en el màrqueting es fa augmentar la predisposició de la companyia a integrar agents particulars en l'entorn de negoci en el desenvolupament del procés d'innovació i a col·laborar-hi, de manera que es millora el grau d'adaptació del nou producte a les demandes del mercat.

Conversation is the Key : A Short History of Smarthistory.org

Smarthistory.org is a proven, sustainable model for open educational resources in the Humanities. We discuss lessons learned during its agile development. Smarthistory.org is a free, creative-commons licensed, multi-media web-book designed as a dynamic enhancement or substitute for the traditional art history textbook. It uses conversation instead of the impersonal voice of the typical textbook in-order to reveal disagreement, emotion, and the experience of looking. The listener remains engaged with both the content and the interaction of the speakers. These conversations model close looking and a willingness to encounter and engage the unfamiliar. Smarthistory takes the inherent dialogic and multimedia nature of the web and uses it as a pedagogical method. This extendable Humanities framework uses an open-source content management system making Smarthistory inexpensive to create, and easy to manage and update. Its chronological timeline/chapter-based format integrates new contributions into a single historical framework, a structure applicable across the Humanities.

The transcription factor PHR1 plays a key role in the regulation of sulfate shoot-to-root flux upon phosphate starvation in Arabidopsis.

Background: Sulfate and phosphate are both vital macronutrients required for plant growth and development. Despite evidence for interaction between sulfate and phosphate homeostasis, no transcriptional factor has yet been identified in higher plants that affects, at the gene expression and physiological levels, the response to both elements. This work was aimed at examining whether PHR1, a transcription factor previously shown to participate in the regulation of genes involved in phosphate homeostasis, also contributed to the regulation and activity of genes involved in sulfate inter-organ transport. Results: Among the genes implicated in sulfate transport in Arabidopsis thaliana, SULTR1;3 and SULTR3;4 showed up-regulation of transcripts in plants grown under phosphate-deficient conditions. The promoter of SULTR1;3 contains a motif that is potentially recognizable by PHR1. Using the phr1 mutant, we showed that SULTR1;3 up regulation following phosphate deficiency was dependent on PHR1. Furthermore, transcript up regulation was found in phosphate-deficient shoots of the phr1 mutant for SULTR2;1 and SULTR3;4, indicating that PHR1 played both a positive and negative role on the expression of genes encoding sulfate transporters. Importantly, both phr1 and sultr1;3 mutants displayed a reduction in their sulfate shoot-to-root transfer capacity compared to wild-type plants under phosphate-deficient conditions. Conclusions: This study reveals that PHR1 plays an important role in sulfate inter-organ transport, in particular on the regulation of the SULTR1;3 gene and its impact on shoot-to-root sulfate transport in phosphate-deficient plants. PHR1 thus contributes to the homeostasis of both sulfate and phosphate in plants under phosphate deficiency. Such a function is also conserved in Chlamydomonas reinhardtii via the PHR1 ortholog PSR1.