Éditeur(s) : HAL CCSD
Résumé : International audience
The Glaser-Eglinton reaction between either two C or N propargylglycine (Pra or NPra) amino acids, in the presence of copper(II), led to cyclic hexa- and octapeptides constrained by a butadiyne bridge. The on-resin cyclization conditions were analyzed and optimized. The consequences of this type of constraint on the three dimensional structure of these hexapeptides and octapeptides were analyzed in details by NMR and molecular dynamics. We show that stabilized short cyclic peptides could be readily prepared via the Glaser oxidative coupling either with a chiral (Pra), or achiral (NPra) residue. The 1,3-butadiyne cyclization, along with disulfide bridged and lactam cyclized hexapeptides expands the range of constrained peptides that will allow exploring the breathing of amino acids around a β-turn structure.
Bioorganic and Medicinal Chemistry

hal-01091920
https://hal.archives-ouvertes.fr/hal-01091920
PUBMED : 25456082
DOI : 10.1016/j.bmc.2014.10.026

Éditeur(s) : HAL CCSD American Association for the Advancement of Science
Résumé :  
Amazon forests are a key but poorly understood component of the global carbon cycle. If, as anticipated, they dry this century, they might accelerate climate change through carbon losses and changed surface energy balances. We used records from multiple long-term monitoring plots across Amazonia to assess forest responses to the intense 2005 drought, a possible analog of future events. Affected forest lost biomass, reversing a large long-term carbon sink, with the greatest impacts observed where the dry season was unusually intense. Relative to pre-2005 conditions, forest subjected to a 100-millimeter increase in water deficit lost 5.3 megagrams of aboveground biomass of carbon per hectare. The drought had a total biomass carbon impact of 1.2 to 1.6 petagrams (1.2 × 1015 to 1.6 × 1015 grams). Amazon forests therefore appear vulnerable to increasing moisture stress, with the potential for large carbon losses to exert feedback on climate change.
ISSN: 0036-8075

hal-01032111
https://hal.archives-ouvertes.fr/hal-01032111
DOI : 10.1126/science.1164033

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : While Amazonian forests are extraordinarily diverse, the abundance of trees is skewed strongly towards relatively few 'hyperdominant' species. In addition to their diversity, Amazonian trees are a key component of the global carbon cycle, assimilating and storing more carbon than any other ecosystem on Earth. Here we ask, using a unique data set of 530 forest plots, if the functions of storing and producing woody carbon are concentrated in a small number of tree species, whether the most abundant species also dominate carbon cycling, and whether dominant species are characterized by specific functional traits. We find that dominance of forest function is even more concentrated in a few species than is dominance of tree abundance, with only ≈1% of Amazon tree species responsible for 50% of carbon storage and productivity. Although those species that contribute most to biomass and productivity are often abundant, species maximum size is also influential, while the identity and ranking of dominant species varies by function and by region.
ISSN: 2041-1723

hal-01204225
https://hal.archives-ouvertes.fr/hal-01204225
DOI : 10.1038/ncomms7857
PRODINRA : 305614
PUBMED : 25919449

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Aim To examine variation in the phylogenetic diversity (PD) of tree communities across geographical and environmental gradients in Amazonia.Location Two hundred and eighty-three c.1ha forest inventory plots from across Amazonia.Methods We evaluated PD as the total phylogenetic branch length across species in each plot (PDss), the mean pairwise phylogenetic distance between species (MPD), the mean nearest taxon distance (MNTD) and their equivalents standardized for species richness (ses.PDss, ses.MPD, ses.MNTD). We compared PD of tree communities growing (1) on substrates of varying geological age; and (2) in environments with varying ecophysiological barriers to growth and survival.Results PDss is strongly positively correlated with species richness (SR), whereas MNTD has a negative correlation. Communities on geologically young- and intermediate-aged substrates (western and central Amazonia respectively) have the highest SR, and therefore the highest PDss and the lowest MNTD. We find that the youngest and oldest substrates (the latter on the Brazilian and Guiana Shields) have the highest ses.PDss and ses.MNTD. MPD and ses.MPD are strongly correlated with how evenly taxa are distributed among the three principal angiosperm clades and are both highest in western Amazonia. Meanwhile, seasonally dry tropical forest (SDTF) and forests on white sands have low PD, as evaluated by any metric.Main conclusions High ses.PDss and ses.MNTD reflect greater lineage diversity in communities. We suggest that high ses.PDss and ses.MNTD in western Amazonia results from its favourable, easy-to-colonize environment, whereas high values in the Brazilian and Guianan Shields may be due to accumulation of lineages over a longer period of time. White-sand forests and SDTF are dominated by close relatives from fewer lineages, perhaps reflecting ecophysiological barriers that are difficult to surmount evolutionarily. Because MPD and ses.MPD do not reflect lineage diversity per se, we suggest that PDss, ses.PDss and ses.MNTD may be the most useful diversity metrics for setting large-scale conservation priorities.
ISSN: 1366-9516

hal-01557462
https://hal.univ-lorraine.fr/hal-01557462
DOI : 10.1111/ddi.12357

Éditeur(s) : HAL CCSD CNRS éditions
Résumé : International audience
Die antike Siedlung von Mandeure und Mathay (Epomanduodurum), welche durch ihre Größe und ihre monumentale Ausstattung als die zweitwichtigste Stadt der Sequaner hinter der Civitashauptstadt Besançon betrachtet wird, ist Gegenstand eines interdisziplinarischen Forschungsprogramms. Dieser Artikel stellt eine Bilanz der Ergebnisse der zwischen 2001 und 2004 durchgeführten Forschungen dar. Im Mittelpunkt der Forschungen der ersten Phase stand der zentralen Teil der Siedlung mit dem Bereich Heiligtum-Theater-spätrömische Befestigung, der für die Problematik der Entstehung, der Entwicklung und dem Ende der römischen Besiedlung besonders interessant ist. Verschiedene, sich ergänzende Projekte wurden eingeleitet: Erforschung des alten Dokumentarbestandes, geophysikalische Prospektionen, geoarchäologische Sondierungen, Plangrabungen, architektonische Untersuchunge. Durch diese Projekte war es möglich, die Kenntnisse über die drei wichtigen Großbauten (Heiligtum-Theater-spätrömische Befestigung) grundsätzlich zu vertiefen und insbesondere die geophysikalischen Prospektionsergebnisse lassen in bemerkenswerter Weise einen dichten Baubestand dieses Stadtteils erkennen. Schließlich konnte die Funktion und die Entwicklung der Flußebene des Doubs in diesem Bereich besser verstanden werden als auch die Art und Weise in welcher die antike Monumentalanlage in diesen einzigartigen natürlichen Rahmen einbezogen wurde.
Since 2001, a collective pluridisciplinary research programme is being undertaken on the antique town of Epomanduodurum in the communes of Mandeure and Mathay. This site is considered like the second one of the Sequani, for its dimensions and the monuments, after the civitas capital, Besançon. This article is an assessment of the investigations conducted between 2001 and 2004. During this period, the central part of the site was studied (sanctuary, theatre, Late fortification area), considered as the most significant for the question of the birth, development and decline of the town. Various complementary approaches have been carried out: study of archives, geophysical and geoarchaeological survey, extent excavations, architectural analyses. They lead to a better understanding of the three main buildings (the Celtic and Gallo-Roman sanctuary, the theatre of the Principate, the Late Antique fortification) and they add considerable informations about the pattern of settlement of this area; so it is possible to detect more precisely the spatial organization and finally to understand how the alluvial plain of the Doubs river was functioning and how the monumental complex has been integrated in such a peculiar landscape.
L'agglomération antique d'Epomanduodurum, située sur les communes de Mandeure et Mathay, et considérée comme la seconde du pays séquane par la taille et la parure monumentale, derrière la capitale de cité, Besançon, fait l'objet d'un programme collectif de recherche, pluridisciplinaire, depuis 2001. Cet article dresse un bilan des résultats des fouilles réalisées entre 2001 et 2004. Dans cette première phase, les investigations ont porté principalement sur la partie centrale du site (secteur sanctuaire-théâtrefortification tardive), perçue comme particulièrement intéressante pour la problématique de la naissance, du développement et du déclin de l'agglomération. Différentes approches complémentaires ont été lancées : étude du fond documentaire ancien, prospections géophysiques, sondages géoarchéologiques, fouilles extensives, études architecturales. Elles ont permis d'approfondir la connaissance des trois principaux édifices (sanctuaire laténien et gallo-romain, théâtre du Haut-Empire, fortification du Bas-Empire), de compléter de façon très notable la trame de l'occupation de ce secteur, et donc d'en mieux percevoir l'organisation spatiale, enfin de mieux comprendre le fonctionnement de la plaine alluviale du Doubs et l'insertion dans ce contexte naturel particulier d'un complexe monumental antique.
ISSN: 0016-4119

halshs-00718356
https://halshs.archives-ouvertes.fr/halshs-00718356

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
AIMS: Virus detection has often been difficult due to a low concentration in water. In this study, we developed a new procedure based on concentration of virus particles on an innovative support: poly-L-lysine dendrigrafts (DGL), coupled with directed nucleic acid extraction and real-time PCR quantification. METHODS AND RESULTS: This method was evaluated using the bacteriophage MS2 as a model virus. This virus exhibited the size and structural properties of human pathogenic enteric viruses and has often been used to assess new supports of concentration. Moreover, this bacteriophage is also a faecal contamination indicator. In this study, many water filtration conditions were tested (volume of water, concentration, etc.), and more than 80% of bacteriophage were recovered after filtration on polymer, in most conditions. We demonstrated that the method was linear (slope = 0*99 ± 0*04 and Y intercept when x = -0*02 ± 0*28), valid (as manipulators, tested concentrations, volumes of sample and batch of polymer did not have any influence on concentration) and sensitive (allowing to concentrate up to 16,600-fold 1 l of sample and to detect and quantify down to 750 GC l(-1) and 7500 GC l(-1), respectively). CONCLUSIONS: To conclude, this support exhibits high interest to retain viruses and to allow to detect low concentration of virus in water. SIGNIFICANCE AND IMPACT OF THE STUDY: This study gives valuable advance in the methods of concentration and diagnosis of virus in water.
Journal of Applied Microbiology

hal-00828987
https://hal.archives-ouvertes.fr/hal-00828987
DOI : 10.1111/jam.12209
PUBMED : 23551794

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
Virus detection has often been difficult due to a low concentration in water. In this study, we developed a new procedure based on concentration of virus particles on an innovative support: poly-L-lysine dendrigrafts (DGL), coupled with directed nucleic acid extraction and real-time PCR quantification. Methods and Results: This method was evaluated using the bacteriophage MS2 as a model virus. This virus exhibited the size and structural properties of human pathogenic enteric viruses and has often been used to assess new supports of concentration. Moreover, this bacteriophage is also a faecal contamination indicator. In this study, many water filtration conditions were tested (volume of water, concentration, etc.), and more than 80% of bacteriophage were recovered after filtration on polymer, in most conditions. We demonstrated that the method was linear (slope = 0 99 0 04 and Y intercept when x = 0 02 0 28), valid (as manipulators, tested concentrations, volumes of sample and batch of polymer did not have any influence on concentration) and sensitive (allowing to concentrate up to 16 600-fold 1 l of sample and to detect and quantify down to 750 GC l 1 and 7500 GC l 1, respectively). Conclusions: To conclude, this support exhibits high interest to retain viruses and to allow to detect low concentration of virus in water. Significance and Impact of the Study: This study gives valuable advance in the methods of concentration and diagnosis of virus in water.
Journal of Applied Microbiology

hal-00932328
https://hal.archives-ouvertes.fr/hal-00932328
DOI : 10.1111/jam.12209

Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD American Society of Nephrology
Résumé : International audience
Since the recent publication of data showing favorable outcomes for patients with HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this population. However, reports have documented unexplained reduced allograft survival in these patients. We hypothesized that the unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function. Using electron microscopy and molecular biology, we examined protocol renal transplant biopsies from 19 recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or tubular cells only (62% of recipients). Podocyte infection associated with podocyte apoptosis and loss of differentiation markers as well as a faster decline in allograft function compared with tubular cell infection. In allografts with tubular cell infection, epithelial cells of the proximal convoluted tubules frequently contained abnormal mitochondria, and both patients who developed features of subclinical acute cellular rejection had allografts with tubular cell infection. Finally, we provide a novel noninvasive test for determining HIV-1 infection of the kidney allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In conclusion, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, and this infection might influence graft outcome.
ISSN: 1046-6673

hal-01121764
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121764
DOI : 10.1681/ASN.2013050564
PUBMED : 24309185
PUBMEDCENTRAL : PMC3904571

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0028-646X

hal-01092529
https://hal-agroparistech.archives-ouvertes.fr/hal-01092529

Résumé : En 1999, le risque écologique encouru par les écosystèmes côtiers soumis à la prolifération de la crépidule, Crepidula fornicata, a été pleinement reconnu par la communauté scientifique nationale et internationale. Au niveau national, le Programme National Environnement Côtier (PNEC) et le programme national LITEAU ont tous deux identifié des actions thématiques prioritaires sur la dynamique de prolifération de la crépidule et les interactions crépidule/bivalves exploités. Les actions du LEMAR (UMR 6539 CNRS) sur cette thématique s’inscrivent dans deux projets : 1 - La crépidule : identifier les mécanismes de sa prolifération et caractériser ses effets sur le milieu pour envisager sa gestion. » (LITEAU) 2 - Recrutement, milieu physique et interactions d'espèces en environnement côtier : cas des mollusques » (PNEC ART2) En rade de Brest, l’accent est mis sur l’interaction des cycles biologiques de la crépidule et de la coquille Saint-Jacques. Les objectifs poursuivis en rade de Brest s’articulent en 4 points, dans le cadre de LITEAU : 1- Dynamique de colonisation de la crépidule en rade de Brest : acquisition des paramètres de dynamique de population (caractéristiques du cycle reproducteur, déterminisme du recrutement, dispersion, croissance, sensibilité aux efflorescences toxiques...) ; 2- Impact de cette prolifération sur l’évolution de la nature sédimentaire des zones colonisées et l’enrichissement en matière organique (par le biais de l’activité alimentaire et de la production de biodépôts) ; 3- Modifications engendrées sur les peuplements benthiques dans leur globalité (sites ateliers). La strate à crépidules, au sens biosédimentaire et écologique, verra sa définition affinée et sa dynamique analysée en vue d'obtenir un modèle prévisionnel des évolutions possibles en matière de biodiversité ; 4- Rôle de la crépidule dans le contrôle de la production primaire phytoplanctonique (par le biais des activités de filtration et de production de biodépôts).

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00032/14292/11570.pdf
http://archimer.ifremer.fr/doc/00032/14292/

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112