Vasotocin receptor expression in the brain and pituitary gland during the ovulatory cycle of the fowl

Vasotocin receptors are members of seven transmembrane spanning G-protein associated receptors. Several isoforms have been recognized in mammals and birds. It has been shown that VT-1 expression occurs primarily in the brain while VT-2 expression occurs mainly in the pituitary. There is no current evidence to support that both VTR-1 and -2 are found in a single tissue. Our goal in this experiment was to see if VT-1 and VT-2 receptor mRNA expression varied in known sites of expression over the period of the ovulatory cycle of broiler breeder hens. In order to study potential changes in VT-1 and VT-2 expression, birds were sacrificed at 3 hour intervals over a 24 hour period. Blood samples were drawn. After cervical dislocation, the brain, pituitary, shell gland, and kidney were removed. Plasma was stored at -20ºC prior to determination of corticosterone levels by radioimmuno assays. Isolated mRNA from the brains and the pituitaries was transferred to nylon membranes for northern slot blot analysis. cDNA for VT-1 and VT-2 was used to make random primed cDNA probes. Corticosterone levels significantly increased at 9 hours post oviposition relative to all other times. Neither VT-1 or VT- 2 expression showed any significant variation over the 24 hour cycle. Based on these results, we conclude that VT-1 and VT-2 steady state mRNA levels do not fluctuate dramatically over the ovulatory cycle of broiler breeder hens. Further work on membrane bound receptors and on circadian variations in membrane bound receptors in the brain and pituitary is currently underway of broiler breeder hens

Individual Differences in Notetaking, Summarization, and Learning from Lectures

This study investigated working memory, verbal ability, and prior knowledge as predictors of the quality of: (a) students' notes taken during a lecture; (b) summaries of the lecture written during a review period; and (c) recall of the lecture content. The usefulness of taking notes was considered in terms of quality of summarization and recall of the lecture material for three groups of students who: (a) listened to the lecture, took notes, and reviewed those notes; (b) listened to the lecture and reviewed a set of provided notes; or (c) listened to the lecture, took notes, and then reviewed a set of provided notes. Results indicated that students with higher working memory benefit more from listening to the lecture than listening and taking notes. However, the quality of summaries written was a more powerful predictor of performance than the individual differences students' brought to the task. This study extends previous studies by integrating summarization and lecture learning research and providing new insight into the role of notetaking and its relationship to working memory.La mémoire de travail, l'habileté verbale et les connaissances préalables ont été étudiées pour leur valeur prédictive de la qualité: (a) des notes que prenaient les étudiants pendant le cours; (b) des résumés de cours rédigés pendant une période de révision; et (c) du rappel du contenu de cours. L'utilité de la prise de notes a été évaluée d'après la qualité des résumés et le rappel du contenu de cours chez trois groupes d'étudiants qui: (a) écoutaient le cours, prenaient des notes et les révisaient; (b) écoutaient le cours et révisaient des notes qu 'on leur fournissait; ou (c) écoutaient le cours, prenaient des notes et révisaient ensuite des notes qu'on leur fournissait. Les résultats indiquent que, pour les étudiants qui ont une plus grande mémoire de travail, il est plus profitable de tout simplement écouter le cours que d'écouter et de prendre des notes. Cependant, la qualité des résumés s'est avérée avoir une meilleure valeur prédictive de la performance que le sont les différences individuelles qui se manifestent pendant l'apprentissage. Cette étude contribue aux précédentes en intégrant la recherche sur le résumé et l'apprentissage qui a lieu pendant les cours, ainsi qu'en fournissant de nouvelles idées sur le rôle de la prise de notes et son lien avec la mémoire de travail

Low-dose aspirin for preventing recurrent venous thromboembolism

Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. Methods We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. Results During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P = 0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P = 0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P = 0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P = 0.22) or serious adverse events. Conclusions In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health and Medical Research Council [Australia] and others; Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.)Health Research Council (New Zealand), Australasian Society of Thrombosis and Hemostasis, National Heart Foundation of Australia, Bayer HealthCare, National Health and Medical Research Council (Australia) program grant 103778

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass

AbstractObjective: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the β2 integrin CD11b. Methods: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. Results: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. Conclusions: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptor

CCL2 nitration is a negative regulator of chemokine-mediated inflammation.

Chemokines promote leukocyte recruitment during inflammation. The oxidative burst is an important effector mechanism, this leads to the generation of reactive nitrogen species (RNS), including peroxynitrite (ONOO). The current study was performed to determine the potential for nitration to alter the chemical and biological properties of the prototypical CC chemokine, CCL2. Immunofluorescence was performed to assess the presence of RNS in kidney biopsies. Co-localisation was observed between RNS-modified tyrosine residues and the chemokine CCL2 in diseased kidneys. Nitration reduced the potential of CCL2 to stimulate monocyte migration in diffusion gradient chemotaxis assays (p < 0.05). This was consistent with a trend towards reduced affinity of the nitrated chemokine for its cognate receptor CCR2b. The nitrated chemokine was unable to induce transendothelial monocyte migration in vitro and failed to promote leukocyte recruitment when added to murine air pouches (p < 0.05). This could potentially be attributed to reduced glycosaminoglycan binding ability, as surface plasmon resonance spectroscopy showed that nitration reduced heparan sulphate binding by CCL2. Importantly, intravenous administration of nitrated CCL2 also inhibited the normal recruitment of leukocytes to murine air pouches filled with unmodified CCL2. Together these data suggest that nitration of CCL2 during inflammation provides a mechanism to limit and resolve acute inflammation

Cobalt ions recruit inflammatory cells in vitro through human Toll-like receptor 4

AbstractMetal-on-metal (MoM) hip replacements, often manufactured from a cobalt-chrome alloy, are associated with adverse reactions including soft tissue necrosis and osteolysis. Histopathological analysis of MoM peri-implant tissues reveals an inflammatory cell infiltrate that includes macrophages, monocytes and neutrophils.Toll-like receptor 4 (TLR4) is an innate immune receptor activated by bacterial lipopolysaccharide. Recent studies have demonstrated that cobalt ions from metal-on-metal joints also activate human TLR4, increasing cellular secretion of inflammatory chemokines including interleukin-8 (IL-8, CXCL8) and CCL2. Chemokines recruit immune cells to the site of inflammation, and their overall effect depends on the chemokine profile produced.This study investigated the effect of cobalt on the secretion of inflammatory cytokines CCL20 and IL-6. The chemotactic potential of conditioned media from a cobalt-stimulated human monocyte cell line on primary monocytes and neutrophils was investigated using an in vitro transwell migration assay. The role of TLR4 in observed effects was studied using a small molecule TLR4-specific antagonist.Cobalt ions significantly increased release of CCL2 and IL-6 by MonoMac 6 cells (P<0.001). Conditioned media from cobalt-stimulated cells significantly increased monocyte and neutrophil chemotaxis in vitro (P<0.001). These effects were abrogated by the TLR4 antagonist (P<0.001) suggesting that they occur through cobalt activation of TLR4.This study demonstrates the role of TLR4 in cobalt-mediated immune cell chemotaxis and provides a potential mechanism by which cobalt ions may contribute to the immune cell infiltrate surrounding failed metal hip replacements. It also highlights the TLR4 signalling pathway as a potential therapeutic target in preventing cobalt-mediated inflammation