Evaluation of floristic diversity in urban areas as a basis for habitat management

International audienceQuestions: How can floristic diversity be evaluated in conser‐vation plans to identify sites of highest interest for biodiversity? What are the mechanisms influencing the distribution of species in human‐dominated environments? What are the best criteria to identify sites where active urban management is most likely to enhance floristic diversity?Location: The Hauts‐de‐Seine district bordering Paris, France.Methods: We described the floristic diversity in one of the most urbanized French districts through the inventory of ca. 1000 sites located in 23 habitats. We built a new index of floristic interest (IFI), integrating information on richness, indigeneity, typicality and rarity of species, to identify sites and habitats of highest interest for conservation. Finally, we explored the relationship between site IFI and land use patterns (LUP).Results: We observed a total of 626 vascular plant species. Habitats with highest IFI were typically situated in seminatural environments or environments with moderate human impact. We also showed that neighbouring (urban) structures had a significant influence on the floristic interest of sites: for example, the presence of collective dwellings around a site had a strong negative impact on IFI.Conclusions: Our approach can be used to optimize management in urban zones; we illustrate such possibilities by defining a ‘Site Potential Value’, which was then compared with the observed IFI, to identify areas (e.g. river banks) where better management could improve the district's biodiversity

IRES-based Vector Coexpressing FGF2 and Cyr61 Provides Synergistic and Safe Therapeutics of Lower Limb Ischemia

Due to the lack of an adequate conventional therapy against lower limb ischemia, gene transfer for therapeutic angiogenesis is seen as an attractive alternative. However, the possibility of side effects, due to the expression of large amounts of angiogenic factors, justifies the design of devices that express synergistic molecules in low controlled doses. We have developed an internal ribosome entry site (IRES)–based bicistronic vector expressing two angiogenic molecules, fibroblast growth factor 2 (FGF2), and Cyr61. Through electrotransfer into the ApoE−/− mice hindlimb ischemic muscle model, we show that the IRES-based vector gives more stable expression than either monocistronic plasmid. Furthermore, laser Doppler analysis, arteriography, and immunochemistry clearly show that the bicistronic vector promotes a more abundant and functional revascularization than the monocistronic vectors, despite the fact that the bicistronic system produces 5–10 times less of each angiogenic molecule. Furthermore, although the monocistronic Cyr61 vector accelerates B16 melanoma growth in mice, the bicistronic vector is devoid of such side effects. Our results show an active cooperation of FGF2 and Cyr61 in therapeutic angiogenesis of hindlimb ischemia, and validate the use of IRES-based bicistronic vectors for the coexpression of controlled low doses of therapeutic molecules, providing perspectives for a safer gene therapy of lower limb ischemia

Can Peto\u27s paradox be used as the null hypothesis to identify the role of evolution in natural resistance to cancer? A critical review

BACKGROUND: Carcinogenesis affects not only humans but almost all metazoan species. Understanding the rules driving the occurrence of cancers in the wild is currently expected to provide crucial insights into identifying how some species may have evolved efficient cancer resistance mechanisms. Recently the absence of correlation across species between cancer prevalence and body size (coined as Peto\u27s paradox) has attracted a lot of attention. Indeed, the disparity between this null hypothesis, where every cell is assumed to have an identical probability to undergo malignant transformation, and empirical observations is particularly important to understand, due to the fact that it could facilitate the identification of animal species that are more resistant to carcinogenesis than expected. Moreover it would open up ways to identify the selective pressures that may be involved in cancer resistance. However, Peto\u27s paradox relies on several questionable assumptions, complicating the interpretation of the divergence between expected and observed cancer incidences. DISCUSSIONS: Here we review and challenge the different hypotheses on which this paradox relies on with the aim of identifying how this null hypothesis could be better estimated in order to provide a standard protocol to study the deviation between theoretical/theoretically predicted and observed cancer incidence. We show that due to the disproportion and restricted nature of available data on animal cancers, applying Peto\u27s hypotheses at species level could result in erroneous conclusions, and actually assume the existence of a paradox. Instead of using species level comparisons, we propose an organ level approach to be a more accurate test of Peto\u27s assumptions. SUMMARY: The accuracy of Peto\u27s paradox assumptions are rarely valid and/or quantifiable, suggesting the need to reconsider the use of Peto\u27s paradox as a null hypothesis in identifying the influence of natural selection on cancer resistance mechanisms

Maternal Antibody Transmission in Relation to Mother Fluctuating Asymmetry in a Long-Lived Colonial Seabird: The Yellow-Legged Gull Larus michahellis

Female birds transfer antibodies to their offspring via the egg yolk, thus possibly providing passive immunity against infectious diseases to which hatchlings may be exposed, thereby affecting their fitness. It is nonetheless unclear whether the amount of maternal antibodies transmitted into egg yolks varies with female quality and egg laying order. In this paper, we investigated the transfer of maternal antibodies against type A influenza viruses (anti-AIV antibodies) by a long-lived colonial seabird, the yellow-legged gull (Larus michahellis), in relation to fluctuating asymmetry in females, i.e. the random deviation from perfect symmetry in bilaterally symmetric morphological and anatomical traits. In particular, we tested whether females with greater asymmetry transmitted fewer antibodies to their eggs, and whether within-clutch variation in yolk antibodies varied according to the maternal level of fluctuating asymmetry. We found that asymmetric females were in worse physical condition, produced fewer antibodies, and transmitted lower amounts of antibodies to their eggs. We also found that, within a given clutch, yolk antibody level decreased with egg laying order, but this laying order effect was more pronounced in clutches laid by the more asymmetric females. Overall, our results support the hypothesis that maternal quality interacts with egg laying order in determining the amount of maternal antibodies transmitted to the yolks. They also highlight the usefulness of fluctuating asymmetry as a sensitive indicator of female quality and immunocompetence in birds

Infectious agents in wild bird populations : eco-epidemiology and evolutionary ecology approaches with the Yellow-legged gull (Larus michaellis) in Mediterranean

L'émergence des zoonoses est à relier directement avec les perturbations générées par l'Homme sur son environnement naturel à plus ou moins grande échelle. Sur l'ensemble des zoonoses émergentes chez l'Homme, la majorité provient d'animaux sauvages. L'étude du rôle de la faune sauvage dans la circulation des agents pathogènes est donc cruciale en particulier quand les interfaces faune sauvage/Homme sont fortes. L'objectif de cette thèse a été de comprendre par des approches éco-épidémiologiques à large échelle, la circulation d'agents pathogènes dans les populations d'un oiseau sauvage en contact étroit avec l'Homme, le goéland leucophée (Larus michahellis). Le premier chapitre présente les différentes méthodes utilisées dans la surveillance d'agents pathogènes ainsi que leurs limites lorsqu'elles sont menées en populations naturelles. Ce chapitre met en évidence au travers d'une étude portant sur les virus influenza aviaires, que la quantification des anticorps maternels dans les œufs est un outil efficace. Le second chapitre consiste à élargir l'échelle spatiale de l'étude afin de mettre en évidence plus finement les facteurs éco-épidémiologiques influençant la transmission des virus influenza aviaires dans et entre les populations de goéland leucophée de l'ouest méditerranéen. Enfin, le dernier chapitre repose sur la comparaison des patrons d'expositions obtenus pour des agents pathogènes au mode de transmission vectoriel : les flavivirus. Cette thèse permet de mettre en évidence les patrons d'exposition de certains agents pathogènes (virus influenza aviaire et flavivirus) et d'appréhender les facteurs éco-épidémiologiques potentiellement impliqués dans leurs circulations. Les résultats permettent d'envisager de futurs axes de recherches, nécessaires pour évaluer plus précisément la dispersion de ces virus en Méditerranée.The emergence of zoonotic diseases is directly linked to the noise generated by humans on the natural environment to a greater or lesser extent. Of all the emerging zoonoses in humans, the majority comes from wild animals. The study of the role of wildlife in the circulation of pathogens is crucial, especially when wildlife/human interfaces are prominent. The aim of this thesis is to understand, using large scale eco-epidemiological approaches, the circulation of pathogens in a close to human population of wild bird, the yellow-legged gull (Larus michahellis). The first chapter presents the different methods used in the monitoring of pathogens and their limitations when they are conducted in natural populations. This chapter further highlights, through a study of avian influenza viruses, that the quantification of maternal antibodies in eggs is an effective tool. The second chapter expands the spatial scale of the study to highlight the finer eco-epidemiological factors influencing the transmission of avian influenza viruses within and between populations of Western Mediterranean yellow-legged gull. Finally, the last chapter is based on the comparison of exposition patterns obtained for vectorial transmission mode pathogens: flaviviruses. This thesis highlights patterns of exposure for certain pathogens (avian influenza virus and flaviviruses) and enables the understanding of the eco-epidemiological factors potentially involved in their circulations. The results allow to consider future areas of research needed to more accurately assess the dispersion of these viruses over the Mediterranean

Trade-offs shape the evolution of the vector-borne insect pathogen Xenorhabdus nematophila

International audienceOur current understanding on how pathogens evolve relies on the hypothesis that pathogens' transmission is traded off against host exploitation. In this study, we surveyed the possibility that trade-offs determine the evolution of the bacterial insect pathogen, Xenorhabdus nematophila. This bacterium rapidly kills the hosts it infects and is transmitted from host cadavers to new insects by a nematode vector, Steinernema carpocapsae. In order to detect trade-offs in this biological system, we produced 20 bacterial lineages using an experimental evolution protocol. These lineages differ, among other things, in their virulence towards the insect host. We found that nematode parasitic success increases with bacteria virulence, but their survival during dispersal decreases with the number of bacteria they carry. Other bacterial traits, such as production of the haemolytic protein XaxAB, have a strong impact on nematode reproduction. We then combined the result of our measurements with an estimate of bacteria fitness, which was divided into a parasitic component and a dispersal component. Contrary to what was expected in the trade-off hypothesis, we found no significant negative correlation between the two components of bacteria fitness. Still, we found that bacteria fitness is maximized when nematodes carry an intermediate number of cells. Our results therefore demonstrate the existence of a trade-off in X. nematophila, which is caused, in part, by the reduction in survival this bacterium causes to its nematode vectors

Récepteur des oestrogènes alpha et physiopathologie vasculaire (étude des cibles cellulaires et rôle des fonctions transactivatrices)

L'effet athéroprotecteur des oestrogènes suggéré par les études épidémiologiques et démontré par les études expérimentales contraste avec l'absence de protection cardiovasculaire induite par le traitement hormonal chez les femmes post-ménopausées. Ainsi, il est urgent de comprendre les effets vasculaires des oestrogènes. Des modèles murins de physiopathologie vasculaire nous ont permis de disséquer les mécanismes moléculaires et cellulaires impliqués dans les effets vasculaires de l'oestradiol (E2) et conduisent aux conclusions suivantes : 1) ERa médie la majorité des effets vasculaires de l'E2. 2) Ces effets sont indépendants de la fonction de transactivation AF-1 du ERa à la différence des effets reproducteurs. 3) L'endothélium constitue la cible cellulaire clé de l'action de l'E2 au niveau du vaisseau. En conclusion, ces données expérimentales seront utiles pour développer des Modulateurs Selectifs des Récepteurs des Oestrogènes (SERM).TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology.

International audienceWhereas hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required at both a cellular and molecular level. Both the endothelium and the immuno-inflammatory system play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. E2 promotes beneficial actions on the endothelium such as nitric oxide and prostacyclin production. E2 actions are essentially mediated by two molecular targets: estrogen receptor alpha (ER-alpha) and beta (ER-beta), but the former appears to mediate most of the actions of E2 on the endothelium and on the immune system. ER-alpha modulates target gene transcription through two activation functions (AF), AF-1 and AF-2, even though signalling via ER-alpha located at the plasma membrane (responsible for membrane-initiated steroid signalling (MISS)/(extra-genomic)) can also lead to an indirect effect on gene transcription. Recently, we demonstrated that ER-alpha AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. These results suggest that selective estrogen receptor modulators stimulating ER-alpha with minimal activation of ER-alpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects

Estrogen receptors and endothelium.

International audienceEstrogens, and in particular 17beta-estradiol (E2), play a pivotal role in sexual development and reproduction and are also implicated in a large number of physiological processes, including the cardiovascular system. Both acetylcholine-induced and flow-dependent vasodilation are preserved or potentiated by estrogen treatment in both animal models and humans. Indeed, E2 increases the endothelial production of nitric oxide and prostacyclin and prevents early atheroma through endothelial-mediated mechanisms. Furthermore, whereas it prevents endothelial activation, E2 potentiates the ability of several subpopulations of the circulating or resident immune cells to produce proinflammatory cytokines. The balance between these 2 actions could determine the final effect in a given pathophysiological process. E2 also promotes endothelial healing, as well as angiogenesis. Estrogen actions are essentially mediated by 2 molecular targets: estrogen receptor-alpha (ERalpha) and ERbeta. The analysis of mouse models targeted for ERalpha or ERbeta demonstrated a prominent role of ERalpha in vascular biology. ERalpha directly modulates transcription of target genes through 2 activation functions (AFs), AF-1 and AF-2. Interestingly, an AF-1-deficient ERalpha isoform can be physiologically expressed in the endothelium and appears sufficient to mediate most of the vasculoprotective actions of E2. In contrast, AF-1 is necessary for the E2 actions in reproductive targets. Thus, it appears conceivable to uncouple the vasculoprotective and sexual actions with appropriate selective ER modulators

Recent circulation of west nile virus and potentially other closely related flaviviruses in Southern France

International audienceIn recent years, the number of West Nile virus (WNV) cases reported in horses and humans has increased dramatically throughout the Mediterranean basin. Furthermore, the emergence of Usutu virus (USUV) in Austria in 2001, and its subsequent expansion to Hungary, Spain, Italy, Switzerland, the United Kingdom, and Germany, has given added cause for concern regarding the impact of the spread of flaviviruses on human and animal health in western Europe. Despite frequent detection of WNV and USUV cases in neighboring countries, no case of WNV has been detected in France since 2006 and USUV has never been reported. However, recent investigations focused on detecting the circulation of flaviviruses in France are lacking. We investigated the circulation of WNV and USUV viruses in wild birds in southern France on the basis of a serological survey conducted on a sentinel species, the magpie (Pica pica), in the Camargue area from November, 2009, to December, 2010. We detected WNV-neutralizing antibodies at a high titer (160) in a second-year bird showing recent exposure to WNV, although no WNV case has been detected in humans or in horses since 2004 in the Camargue. In addition, we observed low titers (10 or 20) of USUV-specific antibodies in six magpies, two of which were also seropositive for WNV. Such low titers do not give grounds for concluding that these birds had been exposed to USUV; cross-reactions at low titers may occur between antigenically closely related flaviviruses. But these results urge for further investigations into the circulation of flaviviruses in southern France. They also emphasize the necessity of undertaking epidemiological studies on a long-term basis, rather than over short periods following public health crises, to gain insight into viral dynamics within natural reservoirs