Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 µ/L and it was completely eliminated after 96 h.

Diagnóstico de avarias em máquinas rotativas utilizando a análise de órbitas

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica Perfil Manutenção e Produção

Loss Modelling of Three-Level Inverters controlled with Space Vector Modulation Technique

The objective of this master’s thesis is to investigate the loss behavior of three-level ANPC inverter and compare it with conventional NPC inverter. The both inverters are controlled with mature space vector modulation strategy. In order to provide the comparison both accurate and detailed enough NPC and ANPC simulation models should be obtained. The similar control model of SVM is utilized for both NPC and ANPC inverter models. The principles of control algorithms, the structure and description of models are clarified. The power loss calculation model is based on practical calculation approaches with certain assumptions. The comparison between NPC and ANPC topologies is presented based on results obtained for each semiconductor device, their switching and conduction losses and efficiency of the inverters. Alternative switching states of ANPC topology allow distributing losses among the switches more evenly, than in NPC inverter. Obviously, the losses of a switching device depend on its position in the topology. Losses distribution among the components in ANPC topology allows reducing the stress on certain switches, thus losses are equally distributed among the semiconductors, however the efficiency of the inverters is the same. As a new contribution to earlier studies, the obtained models of SVM control, NPC and ANPC inverters have been built. Thus, this thesis can be used in further more complicated modelling of full-power converters for modern multi-megawatt wind energy conversion systems.

Développement physiologique des voies visuelles chez le rat normal et chez celui ayant subi des convulsions hyperthermiques

Les neurones des couches superficielles du collicule supérieur et du cortex visuel primaire du rat adulte sont sensibles à de basses fréquences spatiales de haut contraste défilant à des vitesses élevées. Entre les jours post-nataux 27-30 et l’âge adulte, les fréquences temporelles optimales des neurones du cortex visuel primaire augmentent, tandis que leurs seuils de contraste diminuent. Cependant, les fréquences spatiales optimales, les valeurs de résolution spatiale et les bandes passantes spatiales de ces neurones sont, dès l’ouverture des paupières, similaires à celles observées chez le rat adulte. Ces profils de réponse neuronale suggèrent que les projections rétino-colliculaires et rétino-géniculo-corticales sont essentiellement issues de neurones ganglionnaires rétinofuges magnocellulaires et koniocellulaires. Les neurones du cortex visuel primaire du rat ayant subi des convulsions hyperthermiques présentent, dès l’ouverture des paupières, de basses fréquences spatiales optimales, de larges bandes passantes directionnelles et temporelles ainsi que des seuils de contraste élevés par rapport aux neurones du rat normal. À l’âge adulte, de basses fréquences temporelles optimales et de larges bandes passantes spatiales sont également observées chez le rat ayant subi des convulsions hyperthermiques. L’altération des profils de réponse des neurones du cortex visuel primaire du rat ayant subi de convulsions hyperthermiques suggère un déséquilibre entre les mécanismes neuronaux excitateurs et inhibiteurs de cette aire corticale. Ces résultats suggèrent également qu’un épisode unique de convulsions fébriles infantiles suffit à altérer le développement des propriétés spatio-temporelles des champs récepteurs des neurones du cortex visuel primaire.

Biomédecine et médecines alternatives : alliance possible ou scission inévitable? : le cas des acupuncteurs à Montréal

Si l’alternative est de nos jours et dans nos sociétés occidentales un concept de plus en plus en vogue, son caractère lui, en demeure pas moins ambigu. En effet, et alors même que nombre de pratiques dites alternatives émergent de part et d’autre de la société, en faire allusion dans certains domaines équivaut à s’affliger soi-même d’une étiquette sur laquelle serait inscrite « New-Age » en caractère gras. Pourtant, son caractère loin d’évoquer cette seule dimension, semble par ailleurs être conséquente d un déséquilibre de plus en plus prégnant au sein même des prérogatives de l’État. Ce mémoire tente donc de rendre compte de ce phénomène tout en investiguant les répercussions de cette asymétrie sur l’intégration de pratiques médicales alternatives au Québec. Ceci dans l’intention non seulement d’explorer davantage la nature de la relation entre médecine alternative et biomédecine, mais aussi afin de poser un nouveau regard sur son expansion. Un regard, lequel permettrait potentiellement de poser les jalons nécessaires à un espace de conciliation entre les médecines, lequel découlerait alors d’un nouvel équilibre au cœur des prérogatives mêmes de l’État.

Une Fantasy roubaldienne, ou, Nouvelle exploration ludique des potentialités littéraires : essai ; suivi de La Quête du Vortex (création littéraire)

Le Jeu, un phénomène difficile à définir, se manifeste en littérature de différentes manières. Le présent travail en considère deux : l’écriture à contrainte, telle que la pratique l’Oulipo, et l’écriture de l’imaginaire, en particulier les romans de Fantasy française. La première partie de cette étude présente donc, sous forme d’essai, les origines et les visées des deux groupes d’écrivains, mettant en lumière les similitudes pouvant être établies entre eux malgré leurs apparentes différences. Tandis que l’Oulipo cherche des contraintes capables de générer un nombre infini de textes et explore la langue par ce moyen, la Fantasy se veut créatrice de mondes imaginaires en puisant généralement à la source de Tolkien et des jeux de rôle. Il en résulte que le jeu, dans les deux cas, se révèle un puissant moteur de création, que le récit appelle un lecteur-explorateur et qu’il crée une infinité de mondes possibles. Malgré tout, des divergences demeurent quant à leurs critiques, leurs rapports avec le jeu et les domaines extralittéraires, et leurs visées. Considérant ce fait, je propose de combiner les deux styles d’écriture en me servant du cycle des Hortense de Jacques Roubaud (structuré au moyen de la sextine) et des Chroniques des Crépusculaires de Mathieu Gaborit (figure de proue en fantasy « pure »). Ce projet a pour but de combler le fossé restant encore entre les deux groupes. Ainsi, la seconde partie de mon travail constitue une première tentative de réunion des deux techniques d’écriture (à contrainte et de l’imaginaire). Six héros (trois aventuriers et trois mercenaires) partent à la recherche d’un objet magique dérobé à la Reine du Désert et capable de bouleverser l’ordre du monde. Le récit, divisé en six chapitres, rapporte les aventures de ce groupe jusqu’à leur rencontre avec l’ennemi juré de la Reine, un puissant sorcier elfe noir. Chaque chapitre comporte six sections plus petites où sont permutés – selon le mouvement de la sextine – six éléments caractéristiques des jeux de rôles : 1-Une description du MJ (Maître du Jeu) ; 2-Un combat ; 3-Une énigme à résoudre ou un piège à désarmer ; 4-Une discussion entre les joueurs à propos de leurs avatars ; 5-L’acquisition d’un nouvel objet ; 6-Une interaction avec un PNJ (Personnage Non Joueur). Tout au long du texte, des références aux Chroniques des Crépusculaires de Mathieu Gaborit apparaissent, suivant également un ordre sextinien. D’autres allusions, à Tolkien, Queneau, Perec ou Roubaud, agrémentent le roman.

Dissection du processus d’export des ARNm nucléaires par des approches de molécules uniques chez Saccharomyces cerevisae

Enfermer le porteur de l’information génétique dans le noyau a obligée la cellule a créé un système de transport complexe, qui permet l’export d’un ARNm du noyau au cytoplasme. Le mécanisme général de l’export des ARNm est encore mal connu, même si les facteurs principaux ont été découverts il y a longtemps. De récents progrès en microscopie nous ont permis d’étudier directement le comportement des ARNm durant le processus d’export. Durant ma maitrise, nous avons été capables de localiser et suivre des ARNm en temps réel pour la première fois chez Saccharomyces cerevisiae. Nous avons créé un gène rapporteur en mettant le gène GLT1 sous le contrôle du promoteur GAL1. Nous avons aussi marqué l’ARNm de GLT1 avec plusieurs boucles PP7. L’ARNm sera visible après l’attachement de plusieurs protéines PP7-GFP aux boucles. En utilisant la technique d’imagerie en cellules vivantes, nous sommes capable de visualiser et suivre chaque ARNm, depuis son relâchement du site de transcription jusqu’à l’export. Une fois relâché du site de transcription, l’ARNm diffuse librement dans le nucléoplasme, mais une fois à la périphérie nucléaire, il commence à « scanner » l’enveloppe nucléaire avant d’être exporté. Nous avons trouvé que le « scanning » dépend de la présence des Myosin Like Proteins (Mlp1p et Mlp2p), protéines qui forment le panier nucléaire, car suite à la délétion de MLP1 et MLP2, les ARNm n’étaient plus capable de « scanner ». Nous avons également trouvé que la partie C-terminale de Mlp1p était nécessaire au « scanning ». De plus, suite à la délétion du gène TOM1, gène codant pour une ubiquitine ligase, les ARNm ont un comportement similaire aux ARNm d’une souche ∆mlp1/mlp2, suggérant que le « scanning » permet à Tom1p d’ubiquitiner Yra1p, ce qui causera son relâchement de l’ARNm. Également, nous avons montré que les ARNm endogènes MDN1 et CBL2 scannent aussi la périphérie nucléaire. Ensemble, nos résultats suggèrent que le scanning est un processus par lequel passent tout les ARNm nucléaire lorsqu’ils se retrouvent à la périphérie du noyau, pour initier plusieurs étapes de réarrangements nécessaires à leurs export. De plus, nous avons examiné le rôle de Yhr127p, une protéine nouvellement identifiée qui se lie à l’ARN. Après avoir marqué cette protéine avec la GFP, nous avons montré qu’elle forme des foci dans le noyau et que ces derniers vont disparaitre suite à l’arrêt de la transcription. La délétion de YHR127 à conduit à une augmentation de la transcription de quelques gènes spécifiques, mais n’affecte pas la capacité de la cellule à exporter les ARNm. Nos résultats suggèrent que cette protéine joue un rôle dans la régulation de la transcription et/ou dans la stabilité de l’ARNm.

Right to Food, Food Security and Food Aid Under International Law, or the Limits of a right-based approach

The right to food has become a pillar of international humanitarian and human rights law. The increasing number of food-related emergencies and the evolution of the international order brought the more precise notion of food security and made a potential right to receive food aid emerge. Despite this apparent centrality, recent statistics show that a life free from hunger is for many people all over the world still a utopian idea. The paper will explore nature and content of the right to food, food security and food aid under international law in order to understand the reasons behind the substantial failure of this right-centred approach, emphasising the lack of legal effects of many food-related provisions because of excessive moral connotations of the right to be free from hunger. Bearing in mind the three-dimensional nature of food security, the paper will also suggest that all attention has been focused on the availability of food, while real difficulties arise in terms of accessibility and adequacy. Emergency situations provide an excellent example of this unbalance, as the emerging right to receive food aid focus itself on the availability of food, without improving local production and adequacy. Looking at other evolving sectors of international law, such as the protection of the environment, and particularly the safeguard of biological diversity, alternative solutions will be envisaged in order to “feed” the right to food.

Estudio del manejo de residuos sólidos en el Relleno Sanitario Doña Juana con el fin de delinear un borrador de propuesta para el manejo integral de residuos sólidos en la ciudad de Bogotá D.C

Con el presente trabajo se busca realizar una propuesta de solución al sistema de manejo de los residuos sólidos urbanos en el relleno sanitario de Doña Juana en la ciudad de Bogotá, porque los desechos producidos por el consumo humano al no ser tratados de la forma correcta, afectan negativamente a la ciudad, rompen el cirulo vital del desarrollo y desequilibran el medio ambiente. Se realiza un diagnostico histórico al manejo de los residuos sólidos en la ciudad de Bogotá, para poder entender la forma en que el sistema funciona, teniendo en cuenta, sus errores y aciertos, posteriormente por medio Programa 21 de Naciones Unidas, se lleva a cabo el análisis de la información obtenida en el diagnóstico, para que de esta forma, se pueda realizar una propuesta a los problemas identificados en el relleno sanitario de Doña Juana, partiendo de los aspectos económicos, ambientales y sociales.

Four-dimensional data assimilation and balanced dynamics

The problem of spurious excitation of gravity waves in the context of four-dimensional data assimilation is investigated using a simple model of balanced dynamics. The model admits a chaotic vortical mode coupled to a comparatively fast gravity wave mode, and can be initialized such that the model evolves on a so-called slow manifold, where the fast motion is suppressed. Identical twin assimilation experiments are performed, comparing the extended and ensemble Kalman filters (EKF and EnKF, respectively). The EKF uses a tangent linear model (TLM) to estimate the evolution of forecast error statistics in time, whereas the EnKF uses the statistics of an ensemble of nonlinear model integrations. Specifically, the case is examined where the true state is balanced, but observation errors project onto all degrees of freedom, including the fast modes. It is shown that the EKF and EnKF will assimilate observations in a balanced way only if certain assumptions hold, and that, outside of ideal cases (i.e., with very frequent observations), dynamical balance can easily be lost in the assimilation. For the EKF, the repeated adjustment of the covariances by the assimilation of observations can easily unbalance the TLM, and destroy the assumptions on which balanced assimilation rests. It is shown that an important factor is the choice of initial forecast error covariance matrix. A balance-constrained EKF is described and compared to the standard EKF, and shown to offer significant improvement for observation frequencies where balance in the standard EKF is lost. The EnKF is advantageous in that balance in the error covariances relies only on a balanced forecast ensemble, and that the analysis step is an ensemble-mean operation. Numerical experiments show that the EnKF may be preferable to the EKF in terms of balance, though its validity is limited by ensemble size. It is also found that overobserving can lead to a more unbalanced forecast ensemble and thus to an unbalanced analysis.

The neurogenic potential of astrocytes is regulated by inflammatory signals

Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes.

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

The non-coding RNA BC1 is down-regulated in the hippocampus of Wistar Audiogenic Rat (WAR) strain after audiogenic kindling

The aim of this study was to identify molecular pathways involved in audiogenic seizures in the epilepsy-prone Wistar Audiogenic Rat (WAR). For this, we used a suppression-subtractive hybridization (SSH) library from the hippocampus of WARs coupled to microarray comparative gene expression analysis, followed by Northern blot validation of individual genes. We discovered that the levels of the non-protein coding (npc) RNA BC1 were significantly reduced in the hippocampus of WARs submitted to repeated audiogenic seizures (audiogenic kindling) when compared to Wistar resistant rats and to both naive WARs and Wistars. By quantitative in situ hybridization, we verified lower levels of BC1 RNA in the GD-hilus and significant signal ratio reduction in the stratum radiatum and stratum pyramidale of hippocampal CA3 subfield of audiogenic kindled animals. Functional results recently obtained in a BC1-/- mouse model and our current data are supportive of a potential disruption in signaling pathways, upstream of BC1, associated with the seizure susceptibility of WARs. (C) 2010 Elsevier B.V. All rights reserved.

Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to immunomodulation. To this end, Wistar rats (200-250 g) were submitted to 1-hour ischemia and treated with NPCs (4 x 10(6) cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with carboxyfluorescein diacetate succinimydylester (CFSE). Kidneys were harvested for analysis of cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78mg/dl, p < 0.05) and acute tubular necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-CFSE and glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker) mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-beta and TNF-alpha expression and higher anti-inflammatory IL-4 and IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory cytokines (IL-1 beta, TNF-alpha and INF-gamma). Our data suggested that NPC therapy improved renal function by influencing immunological responses. Copyright (C) 2009 S. Karger AG, Basel

Myoglobin-H(2)O(2) catalyzes the oxidation of beta-ketoacids to alpha-dicarbonyls: Mechanism and implications in ketosis

Acetoacetate (AA) and 2-methylacetoacetate (MAA) are accumulated in metabolic disorders such as diabetes and isoleucinemia. Here we examine the mechanism of AA and MAA aerobic oxidation initiated by myoglobin (Mb)/H(2)O(2). We propose a chemiluminescent route involving a dioxetanone intermediate whose thermolysis yields triplet alpha-dicarbonyl species (methylglyoxal and diacetyl). The observed ultraweak chemiluminescence increased linearly on raising the concentration of either Mb (10-500 mu M) or AA (10-100 mM). Oxygen uptake studies revealed that MAA is almost a 100-fold more reactive than AA. EPR spin-trapping studies with MNP/MAA revealed the intermediacy of an alpha-carbon-centered radical and acetyl radical. The latter radical, probably derived from triplet diacetyl, is totally suppressed by sorbate, a well-known quencher of triplet carbonyls. Furthermore, an EPR signal assignable to MNP-AA(center dot) adduct was observed and confirmed by isotope effects. Oxygen consumption and a-dicarbonyl yield were shown to be dependent on AA or MAA concentrations (1-50 mM) and on H(2)O(2) or tert-butOOH added to the Mb-containing reaction mixtures. That ferrylMb is involved in a peroxidase cycle acting on the substrates is suggested by the reaction pH profiles and immunospin-trapping experiments. The generation of radicals and triplet dicarbonyl products by Mb/H(2)O(2)/beta-ketoacids may contribute to the adverse health effects of ketogenic unbalance. (C) 2011 Elsevier Inc. All rights reserved.