Receptor Mechanisms Common to Platelets and Platelet Progenitor Cells

Blood platelets are small, anucleate cells which circulate freely in the cardiovascular system. One of their major physiological functions is concerned with haemostasis - the cessation of bleeding. However, platelets are also involved in the pathological counterpart of haemostasis - thrombosis. Platelets are derived from megakaryocytes which are large nucleated cells located in the bone marrow

Coming of the Global Knowledge Society: Prospects and Promises

Information is becoming one of the vital necessities (if not a basic need) in the contemporary world. With globalization and the growing interdependence of human life, reliable and easy access to information becomes crucial for people who have to adapt their livelihood strategies to continuously changing conditions.  Access to information is a prerequisite for survival in the modern world that is increasingly characterized by global economic and political dynamics. Access alone is, however, not sufficient.  Making adequate use of information (which involves critically organizing a set of given data), transforming such a string of information with the data (again, critically and purposefully organizing these with value-added statements) in order to use it productively at the end -- is just a simplified form of a chain, of what might be called a “global knowledge society”. Creating knowledge requires a set of critical competence, continuum of creativity and capturing emerging opportunity. Being empowered involves being capacitated to making meaningful use of information in view of improving and sustaining one’s livelihood. Empowerment, therefore, is a simple prerequisite for “knowledge-path” and sustainable development as the fundamental paradigm shift for emergence of a global knowledge society.  At the current state of challenges and time of deepening global economic crisis when the overall welfare of many countries is at the risk of long recession and declining standards of living the “knowledge-path” could and should provide certain viable solutions

The Role of Arachidonic Acid and Its Metabolites in Controlling Inositol Lipid Metabolism in Swiss 3T3 Cells

Swiss 3T3 fibroblasts were chosen as a model system to study the role of arachidonic acid and/or its metabolites in controlling sermuM- and PDGF-induced inositol lipid metabolism. (0.01 - 10 muM) caused a rapid stimulation of inositol phospholipid hydrolysis which was maximal within 1-2 minutes of stimulation with the agonist. The level of Ptdlns was not significantly affected by PGF2a. The time course of [3H]-InsP accmuMulation suggests that InsP was not produced directly from Ptdlns, but was formed by the dephosphorylation of InsP2 and InsP3 at least within 1 minute after the PGF2a addition. 1.6 muM PGF2a caused a two-three fold increase in [3H] -PtdA levels, but did not affect the levels of any other major phospholipid measured. Having shown that PGF2a stimulated inositol lipid metabolism in 3T3 cells, it was postulated that the formation of prostaglandins from AA might be intermediatory in the action of PDGF on inositol phospholipid hydrolysis. In order to prove this, it was necessary to be able to inhibit their formation. Surprisingly, the cyclooxygenase inhibitors tested, (flurbiprofen and indomethacin), on their own caused a stimulation of inositol lipid metabolism. This was observed as an increase in [3H]-InsP levels and in [3H]-PtdA levels. The inhibitors had no effect on the levels of any other major phospholipid. The effect of flurbiprofen on inositol lipid metabolism was shown to be dose-related, with 100 muM flurbiprofen producing the maximmuM stimulation. By inhibiting cyclooxygenase activity, it seemed possible that flurbiprofen might have re-directed free AA towards the lipoxygenase pathway and thus the possibility that a stimulatory lipoxygenase metabolite was responsible for the increase in inositol phospholipid hydrolysis was investigated. BW755C, an inhibitor of both cyclooxygenase and lipoxygenase also caused a stimulation of inositol lipid metabolism, in a dose-related manner. The effect was maximal with 100 muM BW755C. Although it remains possible that BW755C did not inhibit all the 1.o. enzymes, it seemed more likely that the stimulation of inositol phospholipid hydrolysis was due to AA itself. Further evidence which suggested this to be the case was that flurbiprofen and BW755C, in a dose-dependent manner caused an increase in the level of free [3H]-AA in the medimuM surrounding the cells. The drugs also caused an increase in the level of [3H] -arachidonyl PtdA. Exogenously applied AA increased the level of [3H]-InsP in a dose-related manner which was maximal with 100 muM AA. This concentration of AA was thought too high to be of physiological significance. However, one contributing factor here was that the majority of the exogenously applied AA bound to albmuMin in the BSS surrounding the cells. In albmuMin-free BSS 0.1 muM AA gave almost an equivalent increase in InsP formation as 100 muM AA in cells surrounded by albmuMin-containing BSS. Also, in experiments where the effects of BW755C and indomethacin on [3H]-AA release and on [3H]-arachidonyl PtdA formation were studied, the results were consistent with the idea that endogenously released AA was binding to albmuMin in the BSS surrounding the cells. Further support for the theory that AA itself stimulated inositol lipid metabolism in 3T3 cells was that flurbiprofen and BW755C were not additive with exogenously applied AA in stimulating inositol phospholipid hydrolysis. This suggests that they have the same pathway of action. Studies were then carried out to investigate the pathway by which AA was liberated. Melittin, a PLA2 activator, stimulated both AA release and inositol lipid metabolism in a dose-related manner. Dexamethasone, an indirect inhibitor of PLA2 abolished the BW755C- and flurbiprofen-induced increase in inositol lipid metabolism in a dose-related manner. These results suggest that the pathway is involved in the liberation of AA from the membrane phospholipids in 3T3 cells. (Abstract shortened by ProQuest.)

Path to eurobonds. Bruegel Working Paper 2012/10, July 2012

This paper discusses proposals for common euro area sovereign securities. Such instruments can potentially serve two functions: in the short-term, stabilize financialmarkets and banks and, in the medium-term, help improve the euro area economic governance framework through enhanced fiscal discipline and risk-sharing. Many questions remain onwhether financial instruments can ever accomplish such goals without bold institutional and political decisions, and,whether, in the absence of such decisions, they can create new distortions. The proposals discussed are also not necessarily competing substitutes; rather, they can be complements to be sequenced along alternative paths that possibly culminate in a fully-fledged Eurobond. The specific path chosen by policymakers should allow for learning and secure the necessary evolution of institutional infrastructures and political safeguards

Regulation of Platelet Function by Cytosolic Free Calcium and Cyclic AMP

Human blood platelet responsiveness can be modulated by a variety of stimulatory and inhibitory agonists. These agents are recognised by specific receptors which presumably are situated on the outer surface of the platelet plasma membrane. Receptors have been characterised for a number of endogenous compounds including adrenaline, ADP, vasopressin, platelet-activating factor, PGI2, PGD2 and adenosine. Platelets are electrically non-excitable, hence, there must exist transduction processes which link events at the cell surface (i. e. agonist-receptor interaction) to the key intracellular reactions which control cellular responsiveness. In platelets, as in many other cell types, it has been established that inositol phospholipid hydrolysis serves as one of the transduction processes that link stimulatory receptor occupancy to cellular activation. Phospholipase C-catalysed hydrolysis of phosphatidylinositol 4,5-bisphosphate yields 1,2-diacylglycerol, an activator of protein kinase C, and inositol (1,4,5) trisphosphate which can mobilise calcium ions from intracellular stores. Inositol phospholipid hydrolysis may also be involved in the agonist-induced influx of calcium ions which also occurs in platelets. Inhibition of platelet reactivity is associated with agonist-induced stimulation of adenylate cyclase activity and increased intracellular levels of cyclic AMP. Cyclic AMP, via activation of cyclic AMP-dependent protein kinase, can modify a variety of platelet intracellular reactions. In vivo platelets may be exposed to combinations of stimulatory and/or inhibitory agonists. Hence, the phenomena of synergism and desensitization, which have been demonstrated in vitro, may occur in vivo and may be of major importance in haemostasis and in the pathogenesis of occlusive vascular disease. This study examined the effects of agonists, alone and in combination, on platelet responsiveness and the putative underlying transduction processes of inositol phospholipid hydrolysis, elevation of cytosolic free calcium concentration [Ca2+]i) and cyclic AMP concentration. Platelet responsiveness was monitored by measuring (a) shape change; (b) aggregation in whole blood (by a single platelet counting method); (c) aggregation in platelet-rich plasma (by two methods: turbidometrically and by counting single platelets); (d) aggregation in gel-filtered platelets and (e) release of dense granule constituents. Stimulation of inositol phospholipid metabolism was assessed as [32P]-Ptd OH formation in platelets prelabelled with [32P] -Pi. Changes in [Ca2+] i were measured using the fluorescent calcium-indicator dye Quin 2 and cyclic AMP levels were measured by radioimmunoassay. 1. In platelet-rich plasma, the single platelet counting method provided a much more sensitive index of aggregation than did the measurement of changes in light transmission in an aggregometer. 2. PAF and vasopressin induced concentration-dependent platelet activation, [32P]-Ptd OH formation and elevation of [Ca2+] ADP-induced platelet activation was associated with elevation of (Ca2+]i but not [32P]-Ptd OH formation. Adrenaline also caused platelet activation but had no direct effect on [Ca2+]i or [32P]-Ptd OH levels. 3. Adrenaline potentiated ADP-, vasopressin- and PAF-induced platelet activation and elevation of Agonist (vasopressin)-induced [32P]-Ptd OH formation was also potentiated. 4. Potentiation of platelet activation by adrenaline may be mediated by enhanced inositol phospholipid hydrolysis and elevation of [Ca2+]i. 5. PGI2, PGE1, 6-keto-PGE1, PGD2 and adenosine induced concentration-dependent elevations in platelet cyclic AMP content. 6. PAF-induced functional platelet responses and transduction processes show differential sensitivity to inhibition by PGD2 and PGI2. A doubling in the platelet cyclic AMP content resulted in abolition of PAF-induced aggregation and ATP secretion, whereas maximal inhibition of shape change, [32P]-Ptd OH formation and elevation of [Ca2+]i required a greater than ten-fold elevation in cyclic AMP. This differential sensitivity of the various responses to inhibition by cyclic AMP suggests that the mechanisms underlying inhibition of PAF-induced aggregation and ATP secretion differ from those underlying shape change. Thus a major component of cyclic AMP-dependent inhibition of PAF-induced aggregation and ATP secretion is mediated by suppression of certain components of the activation process that occur distal to the formation of diacylglycerol or elevation of 7. Inhibitors of adenylate cyclase (adrenaline, ADP) but not vasopressin or PAF, prevented elevation of cyclic AMP content and inhibition of platelet responsiveness and transduction processes by adenylate cyclase stimulants (PGI2, PGD2) but not by other means (e. g. inhibition of phosphodiesterase activity). 8. Activation of protein kinase C by PMA directly inhibited PGD2- but not PGI2-, PGE1-, 6-keto-PGE1- or adenosine-induced cyclic AMP formation. PMA had no effect on the inhibition of cyclic AMP formation by adrenaline

Caractérisation et quantification de la matière organique dissoute dans le complexe des baies d’Hudson et James

La matière organique dissoute est composée de plusieurs molécules provenant de différentes origines, notamment les rivières et l’activité biologique. Celles-ci peuvent avoir une influence considérable sur plusieurs procédés biogéochimiques ainsi que sur le cycle du carbone. Dû à la grande taille du réservoir de matière organique dissoute, de petites variations pourraient avoir un impact considérable sur l’environnement. La DOM contient également des molécules pouvant modifier la biodisponibilité, le transport et la toxicité des contaminants, notamment les thiols dus à leur groupement fonctionnel sulfhydryle. La baie d’Hudson et la baie James sont situées au sud de l’océan Arctique. Leurs positions géographiques ainsi que la quantité de rivières entourant celles-ci les rendent plus vulnérables aux changements climatiques. De plus, l’impact de la contribution en matière organique de la baie James la baie d'Hudson est très peu étudié dans la littérature. L’objectif de ce mémoire consiste à fournir un modèle complet de la circulation et du comportement de la matière organique dans la baie d’Hudson en y incluant l’impact de la baie James. Une méthode de quantification des thiols permettant de les utiliser comme marqueur d’activité biologique

Contributions to the study and modeling of knowledge development systems

Not availabl

Increasing The Agronomic And Economic Value Of Chickpea And Pea

Domestication has had a profound global impact on human history and a wide range of plants. Understanding the advertent and inadvertent effects of domestication on crops has been instrumental in bolstering food security efforts. For instance, by identifying and re-incorporating lost genotypic variation due to domestication, we can increase crop tolerance to biotic and abiotic stressors. With changing climatic conditions and the ever-growing human population, it has become more imperative to increase and fortify agricultural production. My dissertation addresses this topic in two agronomically important legumes: chickpea (Cicer arietinum) and pea (Pisum sativum). My research aims to increase the agronomic and economic value of these legumes to facilitate agricultural production as well as lessen financial burdens to farmers. To accomplish this aim, in chickpea, we identified the physiological and genetic basis of the green-seed market type and identified the effects of domestication on the response to a novel environment. Furthermore, in pea, we investigated phenotypic variation for cover cropping traits using wild accessions, landraces, and modern varieties. In chickpea, we identified that green-seeded chickpea market type was due to a loss of function mutation of the CaStGR1 (carietinum stay-green gene 1) gene involved in chlorophyll catabolism. Additionally, physiological testing in drought conditions revealed this phenotype to be of the “cosmetic” and not the “functional \u27\u27 stay-green variety. Furthermore, nutritional analysis revealed that this trait was associated with a 2-3 fold increase in provitaminogenic carotenoids that are important for human nutrition. Therefore, this green-seeded trait may increase both the economic and nutritional value of chickpea. To identify how domestication has affected chickpea response to novel environments, we took a whole-plant approach and measured above- and below-ground response to increased nitrogen presence in chickpea. Results revealed that domestication has canalized domesticated chickpea response to nitrogen-rich environments. Furthermore, the variable response of wild chickpea to nitrogen illustrated the need for the use of a comprehensive assortment of wild relative accessions to fully discern the effects of domestication on domesticated organisms. Lastly, we coined the terms “rotational” and “intercropping value” and provide a mathematical equation to quantify these terms. We also discuss numerous methods on how to increase these values. To demonstrate these ideas, we measured the rotational values of domesticated and wild pea. We identified that rotational values and cover-cropping traits such as nutrient mobilization and microbial recruitment vary within field pea. These results indicate that field pea could potentially be improved as a rotational partner and that the use of wild relatives in cover cropping research, which has been underutilized, should be considered. Overall, these results illustrate the importance of understanding the effects of domestication and highlights the importance of crop wild relatives as phenotypic reservoirs for crop improvement. Collectively, my research provides insightful information that can facilitate agricultural production at the farming and breeding level