147 research outputs found

    Félix Arnaudin : Chants populaires de la Grande-Lande

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    Ces deux recueils forment les volumes III et IV de l’ensemble des huit volumes des œuvres complètes de Félix Arnaudin, dont le Parc Régional des Landes de Gascogne a entrepris l’édition. Au magnifique album de photos (quelque trois mille plaques de verre), aux Contes (I), aux Proverbes, Dictons, Devinettes, Formulettes, Prières (II), viennent donc s’ajouter ces deux recueils de chants. Doivent suivre le Dictionnaire de la Grande-Lande, également en deux volumes, dont la parution a été retardé..

    A focused antibody library for selecting scFvs expressed at high levels in the cytoplasm

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    <p>Abstract</p> <p>Background</p> <p>Intrabodies are defined as antibody molecules which are ectopically expressed inside the cell. Such intrabodies can be used to visualize or inhibit the targeted antigen in living cells. However, most antibody fragments cannot be used as intrabodies because they do not fold under the reducing conditions of the cell cytosol and nucleus.</p> <p>Results</p> <p>We describe the construction and validation of a large synthetic human single chain antibody fragment library based on a unique framework and optimized for cytoplasmic expression. Focusing the library by mimicking the natural diversity of CDR3 loops ensured that the scFvs were fully human and functional. We show that the library is highly diverse and functional since it has been possible to isolate by phage-display several strong binders against the five proteins tested in this study, the Syk and Aurora-A protein kinases, the αβ tubulin dimer, the papillomavirus E6 protein and the core histones. Some of the selected scFvs are expressed at an exceptional high level in the bacterial cytoplasm, allowing the purification of 1 mg of active scFv from only 20 ml of culture. Finally, we show that after three rounds of selection against core histones, more than half of the selected scFvs were active when expressed <it>in vivo </it>in human cells since they were essentially localized in the nucleus.</p> <p>Conclusion</p> <p>This new library is a promising tool not only for an easy and large-scale selection of functional intrabodies but also for the isolation of highly expressed scFvs that could be used in numerous biotechnological and therapeutic applications.</p

    Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells

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    International audienceABSTRACT: BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer death throughout the world. In this work our aim was to study the role of the phosphoserine aminotransferase PSAT1 in colorectal cancer development. RESULTS: We first observed that PSAT1 is overexpressed in colon tumors. In addition, we showed that after drug treatment, PSAT1 expression level in hepatic metastases increased in non responder and decreased in responder patients. In experiments using human cell lines, we showed that ectopic PSAT1 overexpression in colon carcinoma SW480 cell line resulted in an increase in its growth rate and survival. In addition, SW480-PSAT1 cells presented a higher tumorigenic potential than SW480 control cells in xenografted mice. Moreover, the SW480-PSAT1 cell line was more resistant to oxaliplatin treatment than the non-transfected SW480 cell line. This resistance resulted from a decrease in the apoptotic response and in the mitotic catastrophes induced by the drug treatment. CONCLUSIONS: These results show that an enzyme playing a role in the L-serine biosynthesis could be implicated in colon cancer progression and chemoresistance and indicate that PSAT1 represents a new interesting target for CRC therapy

    8-modified-2\u27-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription

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    The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix &alpha;H in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2&prime;-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2&prime;-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.<br /

    Constraining calcium isotope fractionation (δ44/40Ca) in modern and fossil scleractinian coral skeleton

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    The present study investigates the influence of environmental (temperature, salinity) and biological (growth rate, inter-generic variations) parameters on calcium isotope fractionation (δ44/40Ca) in scleractinian coral skeleton to better constrain this record. Previous studies focused on the δ44/40Ca record in different marine organisms to reconstruct seawater composition or temperature, but only few studies investigated corals. This study presents measurements performed on modern corals from natural environments (from the Maldives for modern and from Tahiti for fossil corals) as well as from laboratory cultures (Centre Scientifique de Monaco). Measurements on Porites sp., Acropora sp., Montipora verrucosa and Stylophora pistillata allow constraining inter-generic variability. Our results show that the fractionation of δ44/40Ca ranges from 0.6 to 0.1‰, independent of the genus or the environmental conditions. No significant relationship between the rate of calcification and δ44/40Ca was found. The weak temperature dependence reported in earlier studies is most probably not the only parameter that is responsible for the fractionation. Indeed, sub-seasonal temperature variations reconstructed by δ18O and Sr/Ca ratio using a multi-proxy approach, are not mirrored in the coral's δ44/40Ca variations. The intergeneric variability and intrageneric variability among the studied samples are weak except for S. pistillata, which shows calcium isotopic values increasing with salinity. The variability between samples cultured at a salinity of 40 is higher than those cultured at a salinity of 36 for this species. The present study reveals a strong biological control of the skeletal calcium isotope composition by the polyp and a weak influence of environmental factors, specifically temperature and salinity (except for S. pistillata). Vital effects have to be investigated in situ to better constrain their influence on the calcium isotopic signal. If vital effects could be extracted from the isotopic signal, the calcium isotopic composition of coral skeletons could provide reliable information on the calcium composition and budget in ocean. Highlights ► Corals cultured in aquaria or from natural environment show the same Ca isotopic composition. ► δ44/40Ca of coral skeleton is independent of depositional setting environment. ► Strong influence of vital effects on coral skeleton δ44/40Ca composition and calcification mechanism

    Cartographie des forĂŞts anciennes de France : objectifs, bilan et perspectives

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    Il y a dix ans démarraient les premiers travaux de vectorisation, à l'échelle régionale, des forêts de la carte d'Etat-Major, en vue de l'établissement d'une carte nationale des forêts à longue continuité de l'état boisé. Où en est-on aujourd'hui ? Nous faisons le point de l'avancement des travaux et en tirons les premiers enseignements, en répondant aux questions suivantes : Quels sont les définitions et concepts sous-jacents à ces travaux ? Pourquoi cartographier les forêts dites "anciennes" ou "récentes" ? L'analyse des institutions ayant réalisé le travail montre que ce sont principalement les milieux de la conservation qui ont été moteurs dans ces travaux. Mais la production et la qualité des produits bois sont aussi concernés par cette cartographie. Le rôle actuel de puits de carbone des forêts françaises ne peut par exemple se comprendre qu'au travers de cette dynamique forestière ancienne. Pourquoi une focalisation sur la première moitié du XIXe siècle comme date de référence ? Que signifie la notion de minimum forestier ? Quelles en sont les limites ? Quels sont les supports de données les plus intéressantes pour cette cartographie ? Pourquoi la carte d'Etat-Major est une source particulière d'information, dans l'objectif de la cartographie des forêts anciennes, parmi la multitude de cartes ou statistiques disponibles à différentes dates et échelles ? Quelles sont les méthodes d'acquisition de la donnée ? Quelle est la précision spatiale des cartes d'occupation du sol obtenues ? Les principaux problèmes posés par l'utilisation de la carte d'Etat-Major seront présentés, ainsi que la façon dont différents projets y ont répondu. Quels résultats ont été obtenus ? Nous reviendrons entre autres sur l'estimation de la surface forestière française à la date de son minimum. Les cartes déjà réalisées, sur 33% du territoire, permettent de dessiner avec précision et de comparer les changements d'occupation du sol dans différentes régions de France, en termes de pourcentage de déboisement, reboisement et taux de forêt ancienne dans la forêt actuelle. Les évolutions du couvert forestier issues d'autres sources non cartographiques sont-elles confirmées ? Le lien avec le type de propriété foncière est particulièrement intéressant à analyser. Dans plusieurs zones de France (Pyrénées, Luberon, Alpes, Lorraine, Nord-Pas-de-Calais...) ont été réalisés des croisements entre ces cartes et les bases de données régionales de relevés floristiques (Inventaire forestier national, conservatoires botaniques). Ce nouveau type d'analyse permet d'identifier rapidement les espèces végétales liées à la continuité de l'état boisé, dites espèces de forêts anciennes, et les traits de vie qui leur sont associés. Nous présenterons une synthèse de ces résultats. Dans la moitié des zones déjà cartographiées, ce sont toutes les occupations du sol anciennes qui ont été numérisées et non seulement les forêts. Nous évoquerons l'intérêt de ce cadastre ancien, au-delà des seules questions forestières, pour le suivi de la dynamique à long terme des prairies, des milieux humides, des vignes ou des milieux urbanisés. Les techniques de vectorisation des occupations anciennes du sol évoluent vers une simplification et une accélération qui laisse présager une fin du travail plus rapide que prévue initialement, parfois au détriment de la qualité. L'extension à la France entière permettra une vision à la fois à petite échelle mais localement précise des mouvements des masses forestières. Nous discuterons les perspectives de recherche et les développements en cours, ouverts par ces progrès

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

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    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
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