Identification de profils métaboliques urinaires reliés à l'exposition au méthylmercure par approche métabonomique

La consommation de produits de la mer s’accompagne d’une exposition élevée au méthylmercure (MeHg) chez la population crie du Nord du Québec. Afin d’obtenir des pistes quant aux conséquences de cette exposition sur la santé de cette population autochtone, une étude de type métabonomique a été réalisée. Cette approche permet d’analyser les variations des concentrations de nombreux métabolites dans les fluides biologiques entre différents groupes de sujets. Par le biais d’analyses statistiques, il est possible d’obtenir de nouvelles informations sur les voies métaboliques altérées par le MeHg et de découvrir des biomarqueurs d’effets précoces générés par cette substance. Pour réaliser cette étude, 83 participants ont été recrutés afin de constituer trois groupes: un groupe de référence du sud du Québec, un groupe de cris montrant des faibles concentrations sanguines en mercure total ( 72 nmol/L). Les échantillons d’urine des participants, obtenus après un jeune de 12 heures, ont été analysés à l’aide d’un chromatographe en phase gazeuse ou liquide couplé à un spectromètre de masse de type temps de vol (LC-TOF-MS et GC-TOF-MS). Des tests bi- et multivariés des données LC-TOF-MS ont permis de cibler 11 biomarqueurs potentiels différents chez l’homme alors que deux l’ont été chez la femme. À partir des données du GC-TOF-MS, quatre candidats ont été observés chez l’homme, incluant l’acide lactique, l’adénosine et le xylose. Des analyses préliminaires par LC-Q-TOF-MS ont été effectuées pour caractériser certains métabolites ciblés. D’autres travaux seront nécessaires afin d’identifier la structure de ces biomarqueurs potentiels

Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs

BACKGROUND: In human, respiratory distress of the neonates, which occurs in prematurity, is prevalent in male. Late in gestation, maturation of type II pneumonocytes, and consequently the surge of surfactant synthesis are delayed in male fetuses compared with female fetuses. Although the presence of higher levels of androgens in male fetuses is thought to explain this sex difference, the identity of genes involved in lung maturation that are differentially modulated according to fetal sex is unknown. We have studied the sex difference in developing mouse lung by gene profiling during a three-day gestational window preceding and including the emergence of mature PTII cells (the surge of surfactant synthesis in the mouse occurs on GD 17.5). METHODS: Total RNA was extracted from lungs of male and female fetal mice (gestation days 15.5, 16.5, and 17.5), converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays (Affymetrix MOE430A). Analysis of data was performed using MAS5.0, LFCM and Genesis softwares. RESULTS: Many genes involved in lung maturation were expressed with no sex difference. Of the approximative 14 000 transcripts covered by the arrays, only 83 genes presented a sex difference at one or more time points between GDs 15.5 and 17.5. They include genes involved in hormone metabolism and regulation (i.e. steroidogenesis pathways), apoptosis, signal transduction, transcriptional regulation, and lipid metabolism with four apolipoprotein genes. Genes involved in immune functions and other metabolisms also displayed a sex difference. CONCLUSION: Among these sexually dimorphic genes, some may be candidates for a role in lung maturation. Indeed, on GD 17.5, the sex difference in surfactant lipids correlates with the sex difference in pulmonary expression of apolipoprotein genes, which are involved in lipid transport. This suggests a role for these genes in the surge of surfactant synthesis. Our results would help to identify novel genes involved in the physiopathology of the respiratory distress of the neonates

Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

<p>Abstract</p> <p>Background</p> <p>Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA) axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production.</p> <p>Methods</p> <p>Expression of genes encoding for corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD) 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH) to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants.</p> <p>Results</p> <p>We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1). Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1) on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed.</p> <p>Conclusions</p> <p>Temporal and spatial modulations of expression of HPA axis-related genes in late gestation are consistent with roles for these genes in lung development. Our data are likely to lead to valuable insights in relation to lung diseases originating from lung immaturity.</p

Gene expression profile of androgen modulated genes in the murine fetal developing lung

<p>Abstract</p> <p>Background</p> <p>Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood.</p> <p>Methods</p> <p>To build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17) and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens.</p> <p>Results</p> <p>Results revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment.</p> <p>Conclusion</p> <p>Our results show clearly that there is a real delay in lung maturation between male and female in this period, the latter pursuing already lung maturation while the proper is not yet fully engaged in the differentiation processes at GD17. In addition, this study provides a list of genes which are under the control of androgens within the lung at the moment of surge of surfactant production in murine fetal lung.</p

The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Effets des pratiques de remise en production des sites dans la région des sables bitumineux sur la croissance du peuplier et de l'épinette blanche

Identifier les principaux facteurs affectant la croissance des arbres sur les sites remis en production après exploitation par l’industrie des sables bitumineux dans le nord de l’Alberta peut nous informer sur ce qui peut être fait pour réduire les délais avant le retour d’un écosystème fonctionnel sur ces sites. Cette étude a examiné le rôle joué par la disponibilité de l’eau, la concentration foliaire des nutriments, de la compétition ainsi que les propriétés chimiques du sol sur la croissance en hauteur de jeunes peupliers faux-tremble et épinettes blanches sur deux types de sol restauré soumis à deux niveaux de fertilisation. Pour fins de comparaison, un site naturel ayant brulé au même moment que la construction du site remis en production a aussi été étudié. Les arbres poussant sur le mélange tourbe-minéral étaient plus grands que ceux du mélange sol forestier-minéral, quoique la différence n’était pas significative dans le cas de l’épinette. La fertilisation n’avait pas d’effet apparent sur la hauteur des arbres sur le mélange sol forestier-minéral et avait un effet négatif sur la hauteur pour les arbres plantés sur le mélange tourbe-minéral. L’utilisation de l’engrais a augmenté le couvert occupé par les plantes concurrentes sur les deux types de sols ce qui, en combinaison avec l’absence d’effet positif sur la hauteur des arbres, suggère que l’effet de la fertilisation est négatif puisqu’elle augmente la compétition pour les ressources sans pour autant favoriser la croissance des deux essences étudiées. Les principaux facteurs affectant la croissance des arbres sur le site d’étude se sont révélés être majoritairement liés à la disponibilité des éléments nutritifs et ne semblent pas être significativement différents entre les deux types de sols. La croissance des drageons de peuplier sur le site naturel n’était pas corrélée avec les variables mesurées ce qui semble indiquer que la hauteur des drageons n’était toujours pas liée aux facteurs environnementaux mesurés après six ans

Présentation

Les finances publiques Contrairement au processus électoral, les finances publiques ne comportent pas une part de jeu qui octroie la victoire au plus habile, au plus fort, au plus charmeur voire au plus convaincant. Les finances publiques sont un instrument au service de l’ensemble de la collectivité. En ce sens, elles doivent être vraies, transparentes, honnêtes, justes et équitables. Pour atteindre ce modèle idéal ou s’en approcher, il faut une convergence harmonieuse et positive de tous le..

Présentation

Les finances publiques Contrairement au processus électoral, les finances publiques ne comportent pas une part de jeu qui octroie la victoire au plus habile, au plus fort, au plus charmeur voire au plus convaincant. Les finances publiques sont un instrument au service de l’ensemble de la collectivité. En ce sens, elles doivent être vraies, transparentes, honnêtes, justes et équitables. Pour atteindre ce modèle idéal ou s’en approcher, il faut une convergence harmonieuse et positive de tous le..

Expression du gène 17β-HSD2 dans le poumon fœtal et le placenta : contrôle de l’action des stéroïdes sexuels

Durant la grossesse, les stéroïdes sexuels pourraient potentiellement nuire au développement fœtal. Deux mécanismes distincts au moins, faisant intervenir la 17β-hydroxystéroïde déshydrogénase- 2 (17β-HSD2), permettraient d’empêcher ces actions indésirables. En s’exprimant dans les fibroblastes pulmonaires et les cellules endothéliales placentaires, la 17β-HSD2 limiterait respectivement l’action de la testostérone et de l’œstradiol, permettant ainsi un développement normal