<p>Oscillations in cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca²⁺]_i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca²⁺]_i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca²⁺]_i in isolated mouse β-cells into sustained elevation. Increased Ca²⁺ entry promoted the reappearance of the slow [Ca²⁺]_i oscillations. The [Ca²⁺]_i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca²⁺]_i oscillations due to periodic entry of Ca²⁺ as well as with transients evoked by mobilization of intracellular stores. The [Ca²⁺]_i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca²⁺]_i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca²⁺]_i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca²⁺ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca²⁺]_i oscillations. Nevertheless, there was an excessive firing of [Ca²⁺]_i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca²⁺]_i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.</p>

<p>This study attests to the fact that disability is an issue in conflict-affected populations, in particular refugees. Refugees with disabilities living in Mayukwayukwa refugee camp also have poor HRQOL similar to other studies. Education was the only variable significantly correlated to the psychological and social domains of the HRQOL. The study highlighted that environmental and personal variables played a role in the determination of health related quality of life among refugees with disabilities.</p>

Oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.

No description available.

To survive, neurons and other eukaryotic cells must rapidly repair (seal) plasmalemmal damage. Such repair occurs by an accumulation of intracellular vesicles at or near the plasmalemmal disruption. Diacylglycerol (DAG)-dependent and cAMP-dependent proteins are involved in many vesicle trafficking pathways. Although recent studies have implicated the signaling molecule cAMP in sealing, no study has investigated how DAG and DAG-dependent proteins affect sealing and, whether pharmacological inhibition of such proteins could promote immediate repair of damaged mammalian axons. To this end, I investigated the role of DAG, protein kinase C (PKC) and other DAG-activated proteins in plasmalemmal sealing in B104 neurons in vitro and rat sciatic nerves in vivo. Using dye exclusion to assess Ca2+-dependent vesicle-mediated sealing of transected neurites of individually identifiable rat hippocampal B104 cells, I now report that, compared to non-treated controls, sealing probabilities and rates are increased by DAG and cAMP analogs that activate PKC and Munc13-1, and protein kinase A (PKA). Sealing is decreased by inhibiting DAG-activated novel protein kinase C isozymes η (nPKCη) and θ (nPKCθ) and, Munc13-1, the PKC effector myristoylated alanine rich PKC substrate (MARCKS) or phospholipase C (PLC). DAG-increased sealing is prevented by inhibiting MARCKS or PKA. Sealing probability is further decreased by simultaneously inhibiting nPKCη, nPKCθ and PKA. Extracellular Ca2+, DAG or cAMP analogs do not affect this decrease in sealing. I also report that applying inhibitors of nPKC and PKA to rat sciatic axons crush-severed in vivo under physiological calcium, do not promote immediate repair by polyethylene glycol (PEG), as assessed by compound action potential conduction and dye diffusion through crush sites. These and other data suggest that DAG increases sealing through MARCKS and that nPKCη, nPKCθ and PKA are all required to seal plasmalemmal damage in B104 neurons, and likely all eukaryotic cells. / text

Les antidépresseurs actuels sont très similaires au niveau de leur mécanisme d’action et sont plus ou moins efficaces. Un des problèmes majeurs est leur long temps de latence à fournir une action thérapeutique dû aux adaptations des sites pré et post synaptiques. Dans un modèle animal, nous avons récemment découvert que l’agoniste RS67333 des récepteurs 5-HT4 était en mesure de produire en trois jours les mêmes effets antidépresseurs qui normalement prennent de deux à trois semaines à apparaître avec les antidépresseurs actuellement disponibles. De plus, nous avons constaté que les effets antidépresseurs de cet agoniste possédaient une résistance à la tolérance. Il y a d’autres agonistes du même récepteur, tel que le prucalopride qui ne produit pas d’effets antidépresseurs comme RS67333. Étant donné que l’efficacité du Prucalopride à stimuler les 5-HT4Rs est similaire sinon plus grande que celle de RS67333, nous avons énoncé l’hypothèse que le récepteur 5-HT4 pourrait adopter différentes conformations actives suite à son activation par différents agonistes. Nous avons ainsi décidé d’explorer les principales réponses fonctionnelles des récepteurs 5-HT4B en observant leurs propriétés de régulation et de signalisation. Nous avons montré que l’isoforme B du récepteur 5-HT4, étant hautement exprimé dans le système limbique, détient une signalisation et une régulation différentes dépendant du ligand activateur. Nos résultats indiquent que chacun des agonistes testés (5-HT, RS67333, ML10302, Zacopride, Prucalopride) modulent distinctivement la production d’AMPc et l’internalisation du récepteur. Les résultats nous ont clairement permis de déterminer que les agonistes possèdent une efficacité et ou puissance différentes les uns par rapport aux autres. De plus, l’ordre d’efficacité des agonistes à moduler la voie de l’AMPc était (Prucalopride > Zacopride = ML10302 = 5-HT > RS67333) et est différente de leur ordre d’efficacité à induire la régulation du récepteur par internalisation (5-HT > Zacopride > Prucalopride > ML10302 = RS67333). Ainsi, nous avons montré que les 5-HT4Rs adoptent des conformations qui sont ligand-spécifiques. Cela implique que la sélectivité fonctionnelle serait un facteur important à considérer dans les mécanismes d’action antidépresseur des agonistes de ce récepteur. / Antidepressants currently available are very similar toward their mechanism of action and are more or less effective. One major problem is their long latency to provide a therapeutic effect due to adaptations of pre and post synaptic locations. In an animal model, we recently discovered that the agonist RS67333 of the 5-HT4 receptors was able to produce in three days the same antidepressant effects that normally take two to three weeks to appear with the currently available antidepressants. In addition, we found that the antidepressant effects of this agonist had a resistance to tolerance. There are others agonists of the same receptor such as prucalopride, which does not produce antidepressant effects as RS67333. Since the effectiveness of prucalopride to stimulate 5-HT4Rs is similar if not greater than RS67333, we stated the hypothesis that the 5-HT4 receptor could adopt different active conformations following its activation by various agonists. We decided to explore the major functional responses of 5-HT4B by observing their regulatory and signaling properties. We showed that the B isoform of the 5-HT4, being highly expressed in the limbic system, has a different signaling and regulation depending on the ligand. Our results indicate that each of the agonists tested (5-HT, RS67333, ML10302, Zacopride, Prucalopride) distinctively modulate cAMP production and receptor internalization. The results have clearly identified that agonists differed in potency and efficacy. Moreover, the order of effectiveness of agonists to modulate the cAMP pathway was (prucalopride> zacopride = 5-HT = ML10302> RS67333) different from their order of effectiveness in inducing receptor regulation by internalization (5-HT> Zacopride> Prucalopride> RS67333 = ML10302). Thus, we have shown that 5-HT4Rs adopt conformations that are ligand-specific. This implies that functional selectivity is an important factor in the mechanisms of antidepressant action of this receptor agonists.

<p>This study attests to the fact that disability is an issue in conflict-affected populations, in particular refugees. Refugees with disabilities living in Mayukwayukwa refugee camp also have poor HRQOL similar to other studies. Education was the only variable significantly correlated to the psychological and social domains of the HRQOL. The study highlighted that environmental and personal variables played a role in the determination of health related quality of life among refugees with disabilities.</p>

SANTRAUKA Sovietinės okupacijos metu žuvo ir nukentėjo apie 350 tūkst. Lietuvos gyventojų. Visų jų atminimui nuo 1941 m. su pertraukomis buvo statomi įvairių tipų paminklai. Tyrimo objektas – rezistencijos dalyvių ir sovietinio genocido aukų įamžinimo paminklais procesas, jo ypatumai ir kylančios problemos, taip pat vietovių ir statinių, įamžintų paminklais, apskaitos ir įpaveldinimo klausimai. Jie iki šiol nenagrinėti ir nėra sulaukę tyrimo. Darbo tikslas – atskleisti Lietuvos gyventojų sovietinio genocido aukų ir rezistencijos dalyvių atminimo įamžinimo ir įpaveldinimo procesus bei su jais susijusias problemas. Tam įgyvendinti yra iškeliami šie uždaviniai: 1. nustatyti paminklų statybos etapus ir statytojų grupes, jas apibūdinti; 2. išsiaiškinti, kaip vykdoma vietovių ir statinių, pažymėtų paminklais, apskaita, koks šių objektų skirstymas; 3. apžvelgti, kaip vykdomi vietovių ir statinių tvarkymo bei įamžinimo darbai; 4. išsiaiškinti, kokios yra įamžinimo ir įpaveldinimo problemos. Tyrimo chronologija – tyrimas pradedamas XX a 5–uoju dešimtmečiu, kadangi jame prasidėjo pirmoji paminklų statymo banga ir įamžinimo darbai. Procesas nėra baigtinis, jis vyksta ir dabar, todėl apsibrėžiame 2006 m. Remiantis darbo tyrimu paminklų statyba sovietinio genocido aukų ir rezistencinio judėjimo dalyvių atminimui Lietuvoje vyko trimis etapais, kur memorialinių vietovių teritorijų tvarkymą, paminklų statybą ir memorialinių statinių ženklinimą vykdė įvairūs žmonės ir organizacijos, kuriuos... [toliau žr. visą tekstą] / SUMMARY OF MASTER’S WORK During the Soviet occupation, around 350,000 Lithuanian residents suffered and died. From 1941 on, with interruptions, monuments of various kinds have been built to commemorate all of them. The subject of this investigation is the process of immortalizing members of the resistance movement and victims of Soviet genocide in monuments, the specific features of and problems encountered in this process, as well as issues concerning the inventory and memorialization of sites and buildings recognized as monuments. These have not been the subject of any study hitherto and have not been the focus of investigation. The goal of this work is to disclose the processes and associated problems of commemorating and memorializing Lithuanian victims of Soviet genocide and members of the resistance. To achieve this goal, the following tasks were formulated: 1. to determine the phases of monument construction and groups of builders, and to characterize them; 2. to explain how inventory of sites and buildings recognized as monuments takes place and how these objects are categorized; 3. to survey how work is carried out for the maintenance and commemoration of sites and buildings; 4. to ascertain the nature of problems involved in commemoration and memorialization. Based on the work of our investigation, the construction of monuments commemorating victims of Soviet genocide and members of the resistance movement took place in three phases in Lithuania, a process in which... [to full text]

The main purpose of dissertation was to be formed economic characteristics district Tabor with appreciation status of the small and middle companies in a given district and possibility their next development. The partial purpose was activity analysis to the local action groups, their comparison and meaning for the development of the small and middle companies. The first step in the processing of the thesis was the study of literature. For the diploma thesis was the method of comparison, the questionnaire and the method of SWOT analysis.

This work is monitored from a professional point of view the area of creativity and its development on students during a summer camp. The theoretical part deals with the problems of creativity, its development and leisure activities. Research section includes a comprehensive weekly program that uses various methods to develop creativity, applied on the high school students during the summer camp activities. The aim of this study was to compare the methods used in terms of their impact on human development, teamwork, communication, creativity and degree of its development. This research showed, that the development of creativity in the teamwork brings a lot of advantages. Especially the level of cooperation, inspiration and humour, that is lived in the group together. In this research is showed that different methods for the development of creativity are developing the components of creativity in different degrees.