ELECTROCORTICAL DYNAMICS OF MOTOR INHIBITORY CONTROL WITH AGING

Motor inhibitory control plays a central role in adaptive behaviors during the entire lifespan. Inhibitory motor control refers to the ability to stop all (global) or a part (selective) of a planned or ongoing motor action. Although the neural processing underlying the global inhibitory control has received much attention from cognitive neuroscientists, brain modulations that occur during selective inhibitory motor control remain unknown. The aim of the present thesis is to investigate the spatio-temporal brain processes of selective inhibitory motor control in young and old adults using high-density electroencephalography. In the first part, we focus on early (preparatory period) spatio-temporal brain processes involved in selective and global inhibitory control in young (study I) and old adults (study II) using a modified Go/No-go task. In study I, we distinguished global from selective inhibition in the early attentional stage of inhibitory control and provided neurophysiological evidence in favor of the combination model. In study II, we showed an under-recruitment of neural resources associated with preservation of performance in old adults during selective inhibition, suggesting efficient cerebral and behavioral adaptations to environmental changes. In the second part, we investigate beta oscillations in the late (post-execution period) spatio-temporal brain processes of selective inhibition during a motor Switching task (i.e., tapping movement from bimanual to unimanual) in young (study III) and old adults (study IV). In study III, we identified concomitant beta synchronization related (i) to sensory reafference processes, which enabled the stabilization of the movement that was perturbed after switching, and (ii) to active inhibition processes that prevented movement of the stopping hand. In study IV, we demonstrated a larger beta synchronization in frontal and parietal regions in old adults compared to young adults, suggesting age-related brain modulations in active inhibition processes. Apart from contributing to a basic understanding of the electrocortical dynamics underlying inhibitory motor control, the findings of the present studies contribute to knowledge regarding the further establishment of specific trainings with aging. -- Le contrôle de l'inhibition motrice joue un rôle central dans les adaptations comportementales quel que soit l'âge. L'inhibition motrice se réfère à la capacité à arrêter entièrement (globale) ou en partie (sélective) une action motrice planifiée ou en cours. Bien que les processus neuronaux sous-jacents de l'inhibition globale aient suscité un grand intérêt auprès des neurosciences cognitives, les modulations cérébrales dans le contrôle de l'inhibition motrice sélective sont encore peu connues. Le but de cette thèse est d'étudier les processus cérébraux spatio-temporels du contrôle de l'inhibition motrice sélective chez les adultes jeunes et âgés en utilisant l'électroencéphalogramme à haute densité. Dans la première partie, nous comparons les processus cérébraux spatio-temporels précoces (préparation motrice) de l'inhibition sélective et globale chez des adultes jeunes (étude I) et âgés (étude II) en utilisant une tâche Go/No-go modifiée. Dans l'étude I, nous avons distingué l'inhibition globale et sélective au niveau des processus attentionnels précoces du contrôle de l'inhibition et nous avons apporté des preuves neurophysiologiques de l'existence d'un modèle de combinaison. Dans l'étude II, nous avons montré une sous-activation neuronale associée à un maintien de la performance dans l'inhibition sélective chez les adultes âgés, suggérant des adaptations cérébrales et comportementales aux contraintes environnementales. Dans la seconde partie, nous examinons les processus cérébraux spatio-temporels tardifs (post-exécution motrice) de l'inhibition sélective pendant une tâche de Switching (tapping bimanuel vers un tapping unimanuel) chez des adultes jeunes (étude III) et âgés (étude IV). Dans l'étude III, nous avons distingué des synchronisations beta liées (i) au traitement des réafférences sensorielles permettant de stabiliser le mouvement perturbé après le switching, et (ii) aux processus d'inhibition active afin d'empêcher les mouvements de la main arrêtée. Dans l'étude IV, cette synchronisation beta était plus forte dans les régions frontales et pariétales chez les âgés par rapport aux jeunes adultes suggérant des modulations cérébrales de l'inhibition active avec l'âge. Outre la contribution fondamentale sur la compréhension des dynamiques électrocorticales dans le contrôle de l'inhibition motrice, les résultats de ces études contribuent à développer les connaissances pour la mise en place de programmes d'entraînements adaptés aux personnes âgées.

Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)(2)cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway.

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

Bodyweight and migration-related differences in motor abilities in preschool children "Ballabeina"

Introduction: Motor abilities in schoolchildren have been decreasing in the last two decades (Bös, 2003, Tomkinson et al., 2003). This may be related to the dramatic increase in overweight and adiposity during the same time period. Children of migrant background are especially affected (Lasserre et al., 2007). But little is known about the relationship between BMI and migration background and motor abilities in preschool children. Methods/Design We carried out a cross-sectional analysis with 665 children (age 5.1 ± 0.6 years; 49.8 % female) of 40 randomly selected kindergarten classes from German and French speaking regions in Switzerland with a high migrant background. We investigated BMI, cardiorespiratory fitness (20 m shuttle run), static (displacement of center of pressure (COP)) and dynamic (balancing forward on a beam) postural control and overall fitness (obstacle course). Results: Of the children, 9.6 % were overweight, 10.5 % were obese (Swiss national percentiles) and 72.8 % were of migrant background (at least one parent born outside of Switzerland). Mean BMI from children of non-migrant background was 15.5 ± 1.1 kg/m2, while migrant children had a mean BMI of 15.8 ± 1.7 kg/m2 (p=0.08). Normal-weight children performed better in cardiorespiratory fitness (3.1 ± 1.4 vs. 2.6 ± 1.1 stages, p<0.001), overall fitness (18.9 ± 4.4 vs. 20.8 ± 4.6 sec, p<0.001) and in dynamic balance (4.9 ± 3.5 vs. 3.8 ± 2.5 steps, p<0.001) compared to overweight and obese children, while the latter had less postural sway (COP: 956 ± 302 vs. 1021 ± 212 mm, p=0.008). There was a clear inverse dose-response relationship between weight status and dynamic motor abilities. There were no significant differences in most tested motor abilities between non-migrant and migrant. The latter performed less well in only one motor test (overall fitness: 20.2 ± 5.2 vs. 18.3 ± 3.5 sec, p<0.001). These findings persisted after adjustment for BMI. Conclusion In preschool children, differences in motor abilities are already present between normal weight and overweight/obese children. However, migrant children demonstrate similar motor abilities compared to non-migrant children for almost all tests, despite their slightly higher BMI.

Myocardial angiogenesis induction with bone protein derived growth factors (animal experiment).

Myocardial angiogenesis induction with vascular growth factors constitutes a potential strategy for patients whose coronary artery disease is refractory to conventional treatment. The importance of angiogenesis in bone formation has led to the development of growth factors derived from bovine bone protein. Twelve pigs (mean weight, 73 +/- 3 kg) were chosen for the study. In the first group (n = 6, growth factor group) five 100 micrograms boluses of growth factors derived from bovine bone protein, diluted in Povidone 5%, were injected in the lateral wall of the left ventricle. In the second group (n = 6, control group), the same operation was performed but only the diluting agent was injected. All the animals were sacrificed after 28 days and the vascular density of the left lateral wall (expressed as the number of vascular structures per mm2) as well as the area of blood vessel profiles per myocardial area analysed were determined histologically with a computerised system. The growth factor group had a capillary density which was significantly higher than that of the control group: 12.6 +/- 0.9/mm2 vs 4.8 +/- 0.5/mm2 (p < 0.01). The same holds true for the arteriolar density: 1 +/- 0.2/mm2 vs 0.3 +/- 0.1/mm2 (p < 0.01). The surface ratios of blood vessel profiles per myocardial area were 4900 +/- 800 micron 2/mm2 and 1550 +/- 400 micron 2/mm2 (p < 0.01) respectively. In this experimental model, bovine bone protein derived growth factors induce a significant neovascularisation in healthy myocardium, and appear therefore as promising candidates for therapeutic angiogenesis.

Disseny i construcció d'un motor 3D en temps real per la Gameboy Advance

El projecte desenvolupat ha tractat l’estudi i disseny d’un motor 3D interactiu a la consolaGame Boy Advance (GBA). La GBA disposa d’un processador ARM7TDMI a 16’78Mhz i no disposa de operacions 3D per-hardware, és una consola lenta en comparació lesque podem trobar al mercat d’avui en dia. Aquest treball, va partir de la construcció d’un prototipus ray-casting per-columna. Després,vàrem adaptar-lo a una estructura de portals i sectors. Més tard,es va introduir el mapeig de sostre/terra i de paisatges. Per últim,vàrem introduir efectes a la renderització per donar més realismeal recorregut del món, com il·luminació, objectes, etc.Tot i que es va estudiar l’arquitectura d’un motor eficient, no estenia prou per arribar a tenir un motor interactiu. Una de lestasques més difícils va ser la part de optimització. Peraconseguir-ho s’ha hagut de substituir operacions a temps realcostoses a temps de execució, replantejar parts de l’algorisme per fer-lo més eficient, entre altres

Simulació mitjançant tècniques CFD d'una culata per al motor del vehicle de baix consum "Àliga-EPS-UdG"

El projecte pretén estudiar i quantificar les restriccions creades al fluid en circular pelsconductes d’admissió i escapament de la culata del motor del vehicle Àliga. L’estudi consta de quatre etapes: estudi de les restriccions actuals dels sistemes d’admissió i escapament; anàlisi dels resultats de la culata de sèrie i proposta de millores aplicables al model real; càlcul de les restriccions creades pels models millorats, i finalment, estudi comparatiu dels resultats obtinguts, interpretant els resultats dels principals paràmetres a analitzar

Motor de cerca iSAC (Servei Intel·ligent d'Atenció Ciutadana Via Web)

El projecte iSAC (Servei Intel·ligent d’Atenció Ciutadana via web) es va iniciar el mes de gener de 2006 amb l’ajut del nou coneixement científic en agents intel·ligents, junt amb l’aplicació de les Tecnologies de la Informació i la Comunicació (TIC) i els cercadors. Actualment, el servei actual d’atenció al ciutadà està composat per dues àrees: l’atenció directa a les oficines i l’atenció telefònica a través del Call Center. Les limitacions de personal i horari d’atenció fan que aquest servei perdi eficàcia.Es vol desenvolupar un producte amb una tecnologia capaç d’ampliar i millorar la capacitat i la qualitat de l’atenció ciutadana en les administracions públiques, sigui quina sigui la seva dimensió. Tot i això, aquest projecte l’explotaran especialment els ajuntaments, als quals la ciutadania s'acosta amb tot tipus de preguntes i dubtes, habitualment no restringides a l'àmbit local.Més concretament, es vol automatitzar a través d’un portal web l’atenció al ciutadà per tal d’obtenir un servei més efectiu

Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development

CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs), these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject.

Integració de llibreries de so posicional amb el motor de render ogre3d

Un videojoc és un joc que involucra a algú la interacció amb un espai d’efectesvisuals en un dispositiu electrònic amb una pantalla i una sèrie de perifèrics quepermeten la interacció. Aconseguir el màxim de realisme es un dels objectiusprincipals dels dissenyadors de videojocs i per això cal integrar en un mateix entorndiferents components tals com: un motor de render, un motor de física, un d’intel•ligència artificial, un motor de so, etc. El motor de so és un dels elements clau delvideojoc, ja que el motor de render pot tenir molts bons gràfics, però sense un sistemade so amb posicionament 3D no es pot apreciar ni gaudir del videojoc en la sevatotalitat.L’objectiu d’aquest projecte és integrar dins del motor gràfic de treball (Ogre3D) un motor de so i convertir el motor de render actual en un motor de videojocs en fase beta.L’objectiu principal d’aquest projecte és implementar un sistema de so completamentintegrat amb la plataforma de Render Ogre3D que permeti de forma senzilla i intuïtivades d’un model de classes més abstracte la fàcil programació dels sons dins delsistema de render.El pla de treball definit per poder assolir els objectius, es divideix en dues fases: fase d’estudi previ on coneixerem les eines que necessitarem per treballar. Entre elles elmotor de render Ogre3D i la fase d’implementació, on ens centrem en els punts d’anàlisi de requeriments, del disseny i de la implementació per a poder integrar les llibreries d’àudio a l’aplicació de la qualpartim (les llibreries de render creades per GameTools)

Twitch potentia induced by two different modalities of neuromuscular electrical stimulation: implications for motor unit recruitment.

INTRODUCTION: We tested the hypothesis that twitch potentiation would be greater following conventional (CONV) neuromuscular electrical stimulation (50-µs pulse width and 25-Hz frequency) compared with wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (1-ms, 100-Hz) and voluntary (VOL) contractions, because of specificities in motor unit recruitment (random in CONV vs. random and orderly in WPHF vs. orderly in VOL). METHODS: A single twitch was evoked by means of tibial nerve stimulation before and 2 s after CONV, WPHF, and VOL conditioning contractions of the plantar flexors (intensity: 10% maximal voluntary contraction; duration: 10 s) in 13 young healthy subjects. RESULTS: Peak twitch increased (P<0.05) after CONV (+4.5±4.0%) and WPHF (+3.3±5.9%), with no difference between the 2 modalities, whereas no changes were observed after VOL (+0.8±2.6%). CONCLUSIONS: Our results demonstrate that presumed differences in motor unit recruitment between WPHF and CONV do not seem to influence twitch potentiation results.