The activation of α1-adrenoceptors is implicated in the antidepressant-like effect of creatine in the tail suspension test

AbstractThe antidepressant-like activity of creatine in the tail suspension test (TST) was demonstrated previously by our group. In this study we investigated the involvement of the noradrenergic system in the antidepressant-like effect of creatine in the mouse TST. In the first set of experiments, creatine administered by i.c.v. route (1μg/site) decreased the immobility time in the TST, suggesting the central effect of this compound. The anti-immobility effect of peripheral administration of creatine (1mg/kg, p.o.) was prevented by the pretreatment of mice with α-methyl-p-tyrosine (100mg/kg, i.p., inhibitor of tyrosine hydroxylase), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), but not by yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist). Creatine (0.01mg/kg, subeffective dose) in combination with subeffective doses of amitriptyline (1mg/kg, p.o., tricyclic antidepressant), imipramine (0.1mg/kg, p.o., tricyclic antidepressant), reboxetine (2mg/kg, p.o., selective noradrenaline reuptake inhibitor) or phenylephrine (0.4μg/site, i.c.v., α1-adrenoceptor agonist) reduced the immobility time in the TST as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of α1-adrenoceptor and that creatine produces synergistic effects in the TST with antidepressants that modulate noradrenaline transporter, suggesting that an improvement in the response to the antidepressant therapy may occur when creatine is combined with these antidepressants. Furthermore, the synergistic effect of creatine (0.01mg/kg, p.o.) and reboxetine (2mg/kg, p.o.) combination was abolished by the α1-adrenoceptor antagonist prazosin, indicating that the antidepressant-like effect of combined therapy is likely mediated by an activation of α1-adrenoceptor

TEMPO NECESSÁRIO PARA NOVILHAS NELORE CRIADAS A PASTO, GANHAREM 210, 240, 270 KG DESDE O NASCIMENTO

O objetivo foi avaliar o número de dias para novilhas da raça Nelore (4.577) ganharem 210, 240 e 270 kg a partir do nascimento, criadas em regime de pasto. Para as análises estatísticas, utilizou-se o método dos quadrados mínimos. O modelo continha os efeitos fixos de mês e ano de nascimento da novilha e a idade da mãe como covariável; como efeito aleatório, touro aninhado dentro de fazenda e o erro. As respostas mostraram que é possível desafiar fêmeas mais jovens, com pesos menores, quando lhes são asseguradas boas condições nutricionais, e assim permitir que seu crescimento não seja interrompido. Days from birth to get 210, 240, 270 kg for nellore heifers on grazing Abstract The objective of this study was to evaluate the number of days for 4,577 nellore heifers raised in regimen of grass to get 210, 240 and 270 kg of weight since the birth. For statistical analyses, the square means method was used. The model contained the fixed effects from helfer´s month and year of birth and the dam´s age as co-variable; as random effect, bull sheltered inside the farm and the error. The results showed that it is possible to challenge younger females, with lower weight, when good nutritional conditions are assured, allowing uninterrupted growth

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis

Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity

Assessing the Societal Impact of Research: The Relational Engagement Approach

Marketing and policy researchers aiming to increase the societal impact of their scholarship should engage directly with relevant stakeholders. For maximum societal effect, this engagement needs to occur both within the research process and throughout the complex process of knowledge transfer. The authors propose that a relational engagement approach to research impact complements and builds on traditional approaches. Traditional approaches to impact employ bibliometric measures and focus on the creation and use of journal articles by scholarly audiences, an important but incomplete part of the academic process. The authors recommend expanding the strategies and measures of impact to include process assessments for specific stakeholders across the entire course of impact, from the creation, awareness, and use of knowledge to societal impact. This relational engagement approach involves the cocreation of research with audiences beyond academia. The authors hope to begin a dialogue on the strategies researchers can use to increase the potential societal benefits of their research