Les travaux de thèse présentés dans ce manuscrit ont pour but d’étudier les effets de différents niveaux d’activité physique, jusqu’à l’inactivité extrême sur des acteurs du dialogue inter-organe comme l’adiponectine et les microARNs, et sur le métabolisme, notamment dans le muscle ou le foie. Nous démontrons que l’inactivité physique extrême, dans le cadre d’un bedrest de 60 jours, augmente les marqueurs de l’inflammation hépatique, prémices du développement d’une stéato-hépatite non alcoolique. Nos données montrent que des exercices réguliers peuvent limiter les altérations métaboliques induites par l’inactivité physique. Nous montrons, ensuite qu’indépendamment des effets de l’activité et l’inactivité physique sur la masse grasse, les concentrations circulantes d’adiponectine sont inversement associées avec le niveau d’activité physique. Nous montrons notamment que les variations des taux circulants d’adiponectine totale avec le niveau d’activité physique sont principalement dû aux variations de la forme de haut poids moléculaire, et ne sont pas expliquées par des variations d’expression de l’adiponectine dans le tissu adipeux ou musculaire. Nous montrons également une relation inverse entre l’insulinémie plasmatique à jeun et les récepteurs de l’adiponectine, et un de ses effecteurs (APPL1) dans le muscle supportant l’amélioration de la sensibilité à l’adiponectine musculaire. Au cours d’une intervention contrastée et modérée sur le niveau d’activité physique chez l’homme et la souris, nous avons pu montrer que la transition d’un statut actif vers inactif augmentait le niveau d’expression de miR-148b dans le muscle, participant à la dégradation du métabolisme. Notre étude de modulation de l’expression de miR-148b in vitro dans les myotubes humains, montre son implication dans la voie de signalisation de l’insuline, et suggère que l’accumulation de miR-148b dans le tissu musculaire peut participer à l’altération de la sensibilité à l’insuline qui est caractéristique des comportements sédentaires persistants. L’ensemble de ces résultats démontrent que l’étude des acteurs de la signalisation inter-organe est cruciale pour comprendre les mécanismes mis en jeu par les comportements actifs et inactifs, et leurs effets sur la santé / Current lifestyle changes, notably sedentary behavior, are associated with chronic diseases, while regular activity improves metabolic functions The purpose of my work is to examine the effects of different level of physical activity, until extreme inactivity on cross-talk mediators, such as adiponectine and microRNAs, and on metabolism, notably in muscle or liver. We demonstrate a significant increase of hepatic markers under severe physical inactivity (60d bed-rest), showing the onset of a development of NASH. Our data support that regular exercise can limit these physical inactivity-induced metabolic alterations. We demonstrate that independently of effects of physical activity and inactivity on fat mass, adiponectin plasma concentrations were negatively related to physical activity level. Our data highlight that variations in total plasma adiponectin with physical activity level are mainly due to changes in HMW adiponectin plasma concentrations, and are unlikely explained by variations in expression of adiponectin in adipose tissue and muscle. We also show an inverse relation between fasting insulin plasma concentrations with both adiponectin receptors, and one of its downstream effector (APPL1) in the muscle, suggesting an improvement of adiponectin muscular sensitivity. During a contrasted and moderate physical activity intervention in human and mice, we show that transition from activity toward inactivity results in muscle miR-148b content increase, leading to muscle metabolism alteration. Our study on miR-148b expression modulation in vitro in human myotubes, show its involvement in insulin signaling pathway in muscle, suggesting that miR-148b accumulation in muscle could participate in the whole body insulin sensitivity degradation, which is a feature of persistent sedentary behavior. Altogether, these results demonstrate that the study of cross-talk actors is crucial to understand the mechanisms involved in active and inactive behaviors, and their effects on health

No description available.

<p>A new FPGA suitable for space applications has just reached the market. To investigate whether there are any possible flaws or limitations similar to those previously seen on FPGAs, an evaluation has to be done. This master thesis contains the evaluation of this new radhard FPGA with focus on possible design limitations and package related electrical phenomena.Areas evaluated: Ground-/VDD bounce, Cross talk, Rise time sensitivit, Power cycling, Power consumption, Place and route tool, Radiation hardnessThis report contains all steps in the evaluation. From method to measurements, comparisons, theory, results and conclusions. In the evaluation work, special effort has been made to develop designs that really stress the FPGA to find potential problems. All problems found are dealt with in this report.Results: Ground-/VDD bounce measurements showed that devices using a fast slew rate resulted in TTL-level violation. However, by separating sensitive signals and SSOs in different I/O banks it is possible to work around the problem. Cross talk measurements has shown that the phenomena causes problems when using a long rise time input with toggling outputs placed next to the signal. Power cycling did not result in any alarming inrush currents. Regular power up showed an unwanted behaviour with pulses on all I/Os right before power on reset kicked in. When comparing the tool value with measurements regarding power consumption it was clear that it differed as much as 40-50%. The FPGA consumes 40-50% more power than what the power calculator tool estimates.</p>

A new FPGA suitable for space applications has just reached the market. To investigate whether there are any possible flaws or limitations similar to those previously seen on FPGAs, an evaluation has to be done. This master thesis contains the evaluation of this new radhard FPGA with focus on possible design limitations and package related electrical phenomena.Areas evaluated: Ground-/VDD bounce, Cross talk, Rise time sensitivit, Power cycling, Power consumption, Place and route tool, Radiation hardnessThis report contains all steps in the evaluation. From method to measurements, comparisons, theory, results and conclusions. In the evaluation work, special effort has been made to develop designs that really stress the FPGA to find potential problems. All problems found are dealt with in this report.Results: Ground-/VDD bounce measurements showed that devices using a fast slew rate resulted in TTL-level violation. However, by separating sensitive signals and SSOs in different I/O banks it is possible to work around the problem. Cross talk measurements has shown that the phenomena causes problems when using a long rise time input with toggling outputs placed next to the signal. Power cycling did not result in any alarming inrush currents. Regular power up showed an unwanted behaviour with pulses on all I/Os right before power on reset kicked in. When comparing the tool value with measurements regarding power consumption it was clear that it differed as much as 40-50%. The FPGA consumes 40-50% more power than what the power calculator tool estimates.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on Feb. 18, 2010). Includes bibliographical references.

The main causative agent of human urinary tract infections is the uropathogenic Escherichia coli (UPEC) pathotype. It may cause disease due to its ability to express a number of bacterial virulence factors. Fimbrial adhesins are particularly important for the initial establishment of infection in the urinary tract. The fimbriae are hair-like structures protruding from the bacterial cell and by attaching to specific receptors in the urinary tract they mediate adherence to different cell types, allowing the bacteria to resist the shear forces from urine flow. The UPEC strains generally carry multiple determinants for fimbrial adhesins. Previous studies have indicated that there is a co-regulation between different fimbrial genes and one factor that has been implicated in this is the PapB protein, acting as a transcriptional regulator of P-fimbrial expression. The PapB protein can be regarded as the prototype of a family of fimbrial regulators that show high homology between different fimbrial operons. One homolog is FocB, regulator of F1C fimbriae. In this study, the role of the FocB protein in the regulation of F1C fimbriae as well as in the co-regulation with other fimbrial genes was investigated. It was observed that FocB binds to DNA, similarly to PapB, in an oligomeric fashion and that PapB and FocB can form hetero-oligomeric complexes, which appear to have a repressive role in the regulation of the F1C fimbriae. In addition, the FocB protein also had a repressive effect on transcription of the fim operon, which encodes theType 1 fimbriae. For further analysis of FocB in vitro, we developed efficient procedures for purification of the protein and established conditions for its crystal formation with the aim to conduct X-ray diffraction studies. By the hanging-drop vapour-diffusion method, we obtained crystals that in the X-ray analysis diffracted sufficiently well to allow modelling of a high resolution structure of FocB. The structural model was considered in relation to the DNA binding properties of the protein. The FocB analysis represents the first structural model of this family of transcriptional factors. This model should aid in further understanding of the roles and functions of these proteins in the regulation of the UPEC fimbrial operons. The complexity of the system, with multiple factors involved in the regulation of fimbrial operons, was revealed in earlier studies of the PapI protein showing that PapI activates transcription of the pap operon as a part of a complex with the global regulator Lrp. However, PapI itself did not appear to bind to DNA and its mode of action has remained unclear. By genetic analyses and in vitro studies we show that PapI may interact also with the α subunit of the RNA polymerase. This finding indicates that PapI might directly interact with the transcriptional apparatus and thus aid in the activation of pap expression. Bacteria are frequently releasing outer membrane vesicles (OMVs) from their surface. We studied the release of the haemolysin toxin from E. coli in connection with formation of OMVs and found that the toxin was tightly associated with the vesicles in an active form. By overproduction of the PapB or PapI regulators in order to maximise the population of bacteria expressing fimbriae, we could detect P fimbriae proteins associated with OMVs that displayed specific adhesion to receptor-coated beads. This suggests a possible scenario in which the vesicles canfunction as directed vehicles of bacterial virulence factors.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Lithium, a drug used for the treatment of bipolar disorder, has been shown to affect different aspects of neuronal development such as neuritogenesis, neurogenesis and survival. The underlying mechanism responsible for lithium's influence on neuronal development, however, still remains to be elucidated. In the present study, we demonstrate that lithium increases the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt) and promotes neurite outgrowth in mouse N2a neuroblastoma cells (N2a). The inactivation of mitogen-activated protein kinase kinase (MEK)/ERKs signaling with a MEK inhibitor inhibits neurite outgrowth, but it enhances Akt activation in lithium-treated N2a cells. Furthermore, the inactivation of phosphoinositide-3-kinase (PI3K)/Akt signaling with a PI3K inhibitor increases both lithium-induced ERKs activation and lithium-induced neurite outgrowth. Taken together, our study suggests that lithium-induced neurite outgrowth in N2a cells is regulated by cross-talk between the MEK/ERKs and PI3K/Akt pathways and requires the activation of the MEK/ERKs signaling.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12831号 / 論医博第2080号 / 新制||医||1005(附属図書館) / 31369 / (主査)教授 川口 義弥, 教授 柳田 素子, 教授 小川 修 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM