Could a satellite-based navigation system (GPS) be used to assess the physical activity of individuals on earth?

OBJECTIVES: To test whether the Global Positioning System (GPS) could be potentially useful to assess the velocity of walking and running in humans. SUBJECT: A young man was equipped with a GPS receptor while walking running and cycling at various velocity on an athletic track. The speed of displacement assessed by GPS, was compared to that directly measured by chronometry (76 tests). RESULTS: In walking and running conditions (from 2-20 km/h) as well as cycling conditions (from 20-40 km/h), there was a significant relationship between the speed assessed by GPS and that actually measured (r = 0.99, P < 0.0001) with little bias in the prediction of velocity. The overall error of prediction (s.d. of difference) averaged +/-0.8 km/h. CONCLUSION: The GPS technique appears very promising for speed assessment although the relative accuracy at walking speed is still insufficient for research purposes. It may be improved by using differential GPS measurement.

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.

Assessing protein stability of the dimeric DNA-binding domain of E2 human papillomavirus 18 with molecular dynamics

The objective of this study is to understand the structural flexibility and curvature of the E2 protein of human papillomavirus type 18 using molecular dynamics (6 ns). E2 is required for viral DNA replication and its disruption could be an anti-viral strategy. E2 is a dimer, with each monomer folding into a stable open-faced β-sandwich. We calculated the mobility of the E2 dimer and found that it was asymmetric. These different mobilities of E2 monomers suggest that drugs or vaccines could be targeted to the interface between the two monomers.

Actin filament dynamics impacts keratinocyte stem cell maintenance.

Cultured human epidermal keratinocyte stem cells (holoclones) are crucial for regenerative medicine for burns and genetic disorders. In serial culture, holoclones progressively lose their proliferative capacity to become transient amplifying cells with limited growth (paraclones), a phenomenon termed clonal conversion. Although it negatively impacts the culture lifespan and the success of cell transplantation, little is known on the molecular mechanism underlying clonal conversion. Here, we show that holoclones and paraclones differ in their actin filament organization, with actin bundles distributed radially in holoclones and circumferentially in paraclones. Moreover, actin organization sets the stage for a differing response to epidermal growth factor (EGF), since EGF signalling induces a rapid expansion of colony size in holoclones and a significant reduction in paraclones. Furthermore, inhibition of PI3K or Rac1 in holoclones results in the reorganization of actin filaments in a pattern that is similar to that of paraclones. Importantly, continuous Rac1 inhibition in holoclones results in clonal conversion and reduction of growth potential. Together, our data connect loss of stem cells to EGF-induced colony dynamics governed by Rac1.

Niche dynamics in space and time.

Niche conservatism, the tendency of a species niche to remain unchanged over time, is often assumed when discussing, explaining or predicting biogeographical patterns. Unfortunately, there has been no basis for predicting niche dynamics over relevant timescales, from tens to a few hundreds of years. The recent application of species distribution models (SDMs) and phylogenetic methods to analysis of niche characteristics has provided insight to niche dynamics. Niche shifts and conservatism have both occurred within the last 100 years, with recent speciation events, and deep within clades of species. There is increasing evidence that coordinated application of these methods can help to identify species which likely fulfill one key assumption in the predictive application of SDMs: an unchanging niche. This will improve confidence in SDM-based predictions of the impacts of climate change and species invasions on species distributions and biodiversity.

FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels.

BACKGROUND FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. OBJECTIVE In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. METHODS The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. RESULTS In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. CONCLUSION The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

Potential impact of a presumed increase in the biting activity of dengue-virus-infected Aedes aegypti (Diptera: Culicidae) females on virus transmission dynamics

Recently, we showed that infection with dengue virus increases the locomotor activity of Aedes aegypti females. We speculate that the observed increased locomotor activity could potentially increase the chances of finding a suitable host and, as a consequence, the relative biting rate of infected mosquitoes. We used a mathematical model to investigate the impact of the increased locomotor activity by assuming that this activity translated into an increased biting rate for infected mosquitoes. The results show that the increased biting rate resulted in dengue outbreaks with greater numbers of primary and secondary infections and with more severe biennial epidemics.

Effect of roscovitine on intracellular calcium dynamics: differential enantioselective responses.

Cyclin-dependent kinases (CDKs) inhibitors have emerged as interesting therapeutic candidates. Of these, (S)-roscovitine has been proposed as potential neuroprotective molecule for stroke while (R)-roscovitine is currently entering phase II clinical trials against cancers and phase I clinical tests against glomerulonephritis. In addition, (R)-roscovitine has been suggested as potential antihypertensive and anti-inflammatory drug. Dysfunction of intracellular calcium balance is a common denominator of these diseases, and the two roscovitine enantiomers (S and R) are known to modulate calcium voltage channel activity differentially. Here, we provide a detailed description of short- and long-term responses of roscovitine on intracellular calcium handling in renal epithelial cells. Short-term exposure to (S)-roscovitine induced a cytosolic calcium peak, which was abolished after stores depletion with cyclopiazonic acid (CPA). Instead, (R)-roscovitine caused a calcium peak followed by a small calcium plateau. Cytosolic calcium response was prevented after stores depletion. Bafilomycin, a selective vacuolar H(+)-ATPase inhibitor, abolished the small calcium plateau. Long-term exposure to (R)-roscovitine significantly reduced the basal calcium level compared to control and (S)-roscovitine treated cells. However, both enantiomers increased calcium accumulation in the endoplasmic reticulum (ER). Consistently, cells treated with (R)-roscovitine showed a significant increase in SERCA activity, whereas (S)-roscovitine incubation resulted in a reduced PMCA expression. We also found a tonic decreased ability to release calcium from the ER, likely via IP3 signaling, under treatment with (S)- or (R)-roscovitine. Together our data revealed that (S)-roscovitine and (R)-roscovitine exert distinct enantiospecific effects on intracellular calcium signaling in renal epithelial cells. This distinct pharmacological profile can be relevant for roscovitine clinical use.

The depuration dynamics of oysters (Crassostrea gigas) artificially contaminated with hepatitis A virus and human adenovirus

Within the country of Brazil, Santa Catarina is a major shellfish producer. Detection of viral contamination is an important step to ensure production quality and consumer safety during this process. In this study, we used a depuration system and ultraviolet (UV) disinfection to eliminate viral pathogens from artificially infected oysters and analysed the results. Specifically, the oysters were contaminated with hepatitis A virus (HAV) or human adenovirus type 5 (HAdV5). After viral infection, the oysters were placed into a depuration tank and harvested after 48, 72 and 96 h. After sampling, various oyster tissues were dissected and homogenised and the viruses were eluted with alkaline conditions and precipitated with polyethylene glycol. The oyster samples were evaluated by cell culture methods, as well as polymerase chain reaction (PCR) and quantitative-PCR. Moreover, at the end of the depuration period, the disinfected seawater was collected and analysed by PCR. The molecular assays showed that the HAdV5 genome was present in all of the depuration time samples, while the HAV genome was undetectable after 72 h of depuration. However, viral viability tests (integrated cell culture-PCR and immunofluorescence assay) indicated that both viruses were inactivated with 96 h of seawater recirculation. In conclusion, after 96 h of UV treatment, the depuration system studied in this work purified oysters that were artificially contaminated with HAdV5 and HAV.

Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity.

Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.

NO rebinding to myoglobin: a reactive molecular dynamics study.

The rebinding of NO to myoglobin after photolysis is studied using the 'reactive molecular dynamics' method. In this approach the energy of the system is evaluated on two potential energy surfaces that include the heme-ligand interactions which change between liganded and unliganded myoglobin. This makes it possible to take into account in a simple way, the high dimensionality of the transition seam connecting the reactant and product states. The dynamics of the dissociated NO molecules are examined, and the geometrical and energetic properties of the transition seam are studied. Analysis of the frequency of recrossing shows that the height of the effective rebinding barrier is dependent on the time after photodissociation. This effect is due mainly to protein relaxation and may contribute to the experimentally observed non-exponential rebinding rate of NO, as has been suggested previously.

Intracellular excision and reintegration dynamics of the ICEclc genomic island of Pseudomonas knackmussii sp. strain B13.

Genomic islands are DNA elements acquired by horizontal gene transfer that are common to a large number of bacterial genomes, which can contribute specific adaptive functions, e.g. virulence, metabolic capacities or antibiotic resistances. Some genomic islands are still self-transferable and display an intricate life-style, reminiscent of both bacteriophages and conjugative plasmids. Here we studied the dynamical process of genomic island excision and intracellular reintegration using the integrative and conjugative element ICEclc from Pseudomonas knackmussii B13 as model. By using self-transfer of ICEclc from strain B13 to Pseudomonas putida and Cupriavidus necator as recipients, we show that ICEclc can target a number of different tRNA(Gly) genes in a bacterial genome, but only those which carry the GCC anticodon. Two conditional traps were designed for ICEclc based on the attR sequence, and we could show that ICEclc will insert with different frequencies in such traps producing brightly fluorescent cells. Starting from clonal primary transconjugants we demonstrate that ICEclc is excising and reintegrating at detectable frequencies, even in the absence of recipient. Recombination site analysis provided evidence to explain the characteristics of a larger number of genomic island insertions observed in a variety of strains, including Bordetella petri, Pseudomonas aeruginosa and Burkholderia.