Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
A relevant and accurate description of three-dimensional (3D) protein structures can be achieved by characterizing recurrent local structures. In a previous study, we developed a library of 120 3D structural prototypes encompassing all known 11-residues long local protein structures and ensuring a good quality of structural approximation. A local structure prediction method was also proposed. Here, overlapping properties of local protein structures in global ones are taken into account to characterize frequent local networks. At the same time, we propose a new long local structure prediction strategy which involves the use of evolutionary information coupled with Support Vector Machines (SVMs). Our prediction is evaluated by a stringent geometrical assessment. Every local structure prediction with a Calpha RMSD less than 2.5 A from the true local structure is considered as correct. A global prediction rate of 63.1% is then reached, corresponding to an improvement of 7.7 points compared with the previous strategy. In the same way, the prediction of 88.33% of the 120 structural classes is improved with 8.65% mean gain. 85.33% of proteins have better prediction results with a 9.43% average gain. An analysis of prediction rate per local network also supports the global improvement and gives insights into the potential of our method for predicting super local structures. Moreover, a confidence index for the direct estimation of prediction quality is proposed. Finally, our method is proved to be very competitive with cutting-edge strategies encompassing three categories of local structure predictions. Proteins 2009. (c) 2009 Wiley-Liss, Inc.
ISSN: 0887-3585

inserm-00348740
http://www.hal.inserm.fr/inserm-00348740
http://www.hal.inserm.fr/inserm-00348740/document
http://www.hal.inserm.fr/inserm-00348740/file/Bornot_Proteins_2009_preprint_version.pdf
http://www.hal.inserm.fr/inserm-00348740/file/inserm-00348740_edited.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The tree model and tree-based methods have played a major, fruitful role in evolutionary studies. However, with the increasing realization of the quantitative and qualitative importance of reticulate evolutionary processes, affecting all levels of biological organization, complementary network-based models and methods are now flourishing, inviting evolutionary biology to experience a network-thinking era. We show how relatively recent comers in this field of study, that is, sequence-similarity networks, genome networks, and gene families–genomes bipartite graphs, already allow for a significantly enhanced usage of molecular datasets in comparative studies. Analyses of these networks provide tools for tackling a multitude of complex phenomena, including the evolution of gene transfer, composite genes and genomes, evolutionary transitions, and holobionts.
ISSN: 0966-842X

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01300043
http://hal.upmc.fr/hal-01300043
http://hal.upmc.fr/hal-01300043/document
http://hal.upmc.fr/hal-01300043/file/Network-Thinking.pdf
DOI : 10.1016/j.tim.2015.12.003

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
Transcriptional regulation by the estrogen receptor-alpha(ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17 beta-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4 alpha BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4 alpha, ER might be required for proper Foxa2 function in this tissue.
ISSN: 0888-8809

hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/file/Changes%20in%20gene%20expression%201%20and%20Estrogen%20Receptor_accepted.pdf
DOI : 10.1210/me.2015-1311

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
We propose a new geometric approach to describe the qualitative dynamics of chemical reactions networks. By this method we identify metastable regimes, defined as low dimensional regions of the phase space close to which the dynamics is much slower compared to the rest of the phase space. These metastable regimes depend on the network topology and on the orders of magnitude of the kinetic parameters. Benchmarking of the method on a computational biology model repository suggests that the number of metastable regimes is sub-exponential in the number of variables and equations. The dynamics of the network can be described as a sequence of jumps from one metastable regime to another. We show that a geometrically computed con-nectivity graph restricts the set of possible jumps. We also provide finite state machine (Markov chain) models for such dynamic changes. Applied to signal transduction models, our approach unravels dynamical and functional * corresponding author capacities of signalling pathways, as well as parameters responsible for speci-ficity of the pathway response. In particular, for a model of TGFβ signalling, we find that the ratio of TGFBR2 to TGFBR1 receptors concentrations can be used to discriminate between metastable regimes. Using expression data from the NCI60 panel of human tumor cell lines, we show that aggressive and non-aggressive tumour cell lines function in different metastable regimes and can be distinguished by measuring the relative concentrations of receptors of the two types.
ISSN: 0303-2647

hal-01379033
https://hal.inria.fr/hal-01379033
https://hal.inria.fr/hal-01379033/document
https://hal.inria.fr/hal-01379033/file/Samal_et_al_Biosystems_final.pdf
DOI : 10.1016/j.biosystems.2016.07.004

Éditeur(s) : HAL CCSD Society for Molecular Biology and Evolution
Résumé : International audience
Complex nongradual evolutionary processes such as gene remodeling are difficult to model, to visualize, and to investigate systematically. Despite these challenges, the creation of composite (or mosaic) genes by combination of genetic segments from unrelated gene families was established as an important adaptive phenomena in eukaryotic genomes. In contrast, almost no general studies have been conducted to quantify composite genes in viruses. Although viral genome mosaicism has been well-described, the extent of gene mosaicism and its rules of emergence remain largely unexplored. Applying methods from graph theory to inclusive similarity networks, and using data from more than 3,000 complete viral genomes, we provide the first demonstration that composite genes in viruses are 1) functionally biased, 2) involved in key aspects of the arm race between cells and viruses, and 3) can be classified into two distinct types of composite genes in all viral classes. Beyond the quantification of the widespread recombination of genes among different viruses of the same class, we also report a striking sharing of genetic information between viruses of different classes and with different nucleic acid types. This latter discovery provides novel evidence for the existence of a large and complex mobilome network, which appears partly bound by the sharing of genetic information and by the formation of composite genes between mobile entities with different genetic material. Considering that there are around 10E31 viruses on the planet, gene remodeling appears as a hugely significant way of generating and moving novel sequences between different kinds of organisms on Earth.
ISSN: 1759-6653

Droits : http://creativecommons.org/licenses/by/
hal-01324848
http://hal.upmc.fr/hal-01324848
http://hal.upmc.fr/hal-01324848/document
http://hal.upmc.fr/hal-01324848/file/Genome%20Biol%20Evol-2014-Jachiet-2195-205.pdf
DOI : 10.1093/gbe/evu168

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: End-Stage renal disease (ESRD) causes considerable morbidity and mortality, and significantly alterspatients’ quality of life. There are very few published data on this problem in the French Overseas territories. Thedevelopment of a registry on end stage renal disease in French Guiana in 2011 allowed to describe the magnitudeof this problem in the region for the first time.Methods: Using data from the French Renal Epidemiology and Information Network registry (R.E.I.N). Descriptivestatistics on quantitative and qualitative variables in the registry were performed on prevalent cases and incidentcases in 2011, 2012 and 2013.Results: French Guiana has one of the highest ESRD prevalence and incidence in France. The two main causes ofESRD were hypertensive and diabetic nephropathies. The French Guianese population had a different demographicprofile (younger, more women, more migrants) than in mainland France. Most patients had at least one comorbidity,predominantly (95.3%) hypertension. In French Guiana dialysis was initiated in emergency for 71.3% of patients versus33% in France (p < 0.001).Conclusion: These first results give important public health information: i) End stage renal disease has a very highprevalence relative to mainland France ii) Patients have a different demographic profile and enter care late in thecourse of their renal disease. These data are closer to what is observed in the Caribbean or in Latin America than inMainland France.
ISSN: 1471-2369

inserm-01567222
http://www.hal.inserm.fr/inserm-01567222
http://www.hal.inserm.fr/inserm-01567222/document
http://www.hal.inserm.fr/inserm-01567222/file/2017%2C%20Rochemont%20-%20End%20stage%20renal%20disease.pdf
DOI : 10.1186/s12882-017-0614-6

Éditeur(s) : HAL CCSD
Résumé : The recent accumulation of genomic sequence data has shown that gene evolution is not strictly tree-Like. Many evolutionary processes, like exon shuffling, gene fusion or nonhomologous recombination remodel genes by creating composite structures that are made from parts with different evolutionary histories. The development of sequence similarity networks provides an analytical framework to study the impact of these processes on molecular evolution, by structuring the resemblance relationships between sequences and by formalizing, in terms of graph theory, the detection of composite genes (intransitive triplets) and gene families (clique minimal separators). The size of current data sets, typically several million sequences, has also required the development of new tools and methods: sequence comparison parallelization, large networks visualization with Louvain communities and large cycles identification. When applied to eukaryotic and viral genome data sets, these methods have shown that composite genes are found throughout cellular organisms and mobile genetic elements. Proportionally, composite genes are more numerous in eukaryotic genomes; in absolute number, they are more numerous in viruses. In the latter, composite genes functional distribution is biased (enrichment of genes families that are essential for the perpetuation of the viral cycle), and the various parts of composite genes sometimes even originate from the genetic material of different viral classes. More generally, the extent of combinatorial processes, by unravelling other evolutionary bonds than homology bonds in the strictest sense, legitimates a pluralistic study of similarity relationships between sequences.
L’accumulation récente de données de séquences génomiques a montré que l’évolution des gènes n’est pas strictement arborescente. De nombreux processus évolutifs, comme l’exon shuffling, la fusion de gènes ou la recombinaison illégitime remodèlent les gènes, créant des structures composites, formées de parties dont les histoires évolutives sont différentes. Le développement de réseaux de similarité de séquences fournit un cadre analytique permettant d’étudier l’impact de ces processus sur l’évolution moléculaire, en structurant les relations de ressemblance entre séquences et en formalisant en termes de graphes la détection de gènes (triplets intransitifs) et de familles de gènes (cliques minimales séparatrices) composites. La taille des jeux de données actuels, de l’ordre de plusieurs millions de séquences, a également requis le développement de nouveaux outils et méthodes : parallélisation des comparaisons de séquences, visualisation de très grands réseaux par simplification en communautés de Louvain et identification de grands cycles. Appliquées à des jeux de données de génomes eucaryotes et viraux, ces méthodes ont démontré la présence de gènes composites dans tout le vivant et les éléments génétiques mobiles. En proportion, les gènes composites sont plus nombreux dans les génomes eucaryotes ; en nombre absolu, ils sont plus nombreux à être portés par des virus. Chez ces derniers, la distribution fonctionnelle des gènes composites est biaisée (enrichissement dans les familles essentielles pour la perpétuation du cycle viral), et les éléments des gènes composites trouvent même parfois leurs origines dans le matériel génétique de classes virales différentes. Plus généralement, l’étendue des processus combinatoires, en révélant des liens évolutionnaires autres que les liens d’homologie au sens fort, justifie une étude pluraliste des relations de similarité entre séquences.
https://tel.archives-ouvertes.fr/tel-01127379

NNT : 2014PA066358
tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379/document
https://tel.archives-ouvertes.fr/tel-01127379/file/2014PA066358.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : While around 20% of the Amazonian forest has been cleared for pastures and agriculture, one fourth of the remaining forest is dedicated to wood production [1] . Most of these production forests have been or will be selectively harvested for commercial timber, but recent studies show that even soon after logging, harvested stands retain much of their tree-biomass carbon and biodiversity [2,3] . Comparing species richness of various animal taxa among logged and unlogged forests across the tropics, Burivalova et al. [4] found that despite some variability among taxa, biodiversity loss was generally explained by logging intensity (the number of trees extracted). Here, we use a network of 79 permanent sample plots (376 ha total) located at 10 sites across the Amazon Basin [5] to assess the main drivers of time-to-recovery of post-logging tree carbon ( Table S1 ). Recovery time is of direct relevance to policies governing management practices (i.e., allowable volumes cut and cutting cycle lengths), and indirectly to forest-based climate change mitigation interventions.
ISSN: 0960-9822

hal-01536542
https://hal.archives-ouvertes.fr/hal-01536542
DOI : 10.1016/j.cub.2015.07.034
PRODINRA : 343217
PUBMED : 26394096

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. METHODS: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. RESULTS: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. CONCLUSIONS: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.
ISSN: 0022-1899

hal-00875299
https://hal.archives-ouvertes.fr/hal-00875299
DOI : 10.1093/infdis/jir211
PUBMED : 21628666

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
DNA sequencing technology is becoming more accessible to a variety of researchers as costs continue to decline. As researchers begin to sequence novel transcriptomes, most of these data sets lack a reference genome and will have to rely on de novo assemblers. Making comparisons across assemblies can be difficult: each program has its strengths and weaknesses, and no tool exists to comparatively evaluate these data sets. We developed software in R, called Sequence Comparative Analysis using Networks (SCAN), to perform statistical comparisons between distinct assemblies. SCAN uses a reference data set to identify the most accurate de novo assembly and the ``good'' transcripts in the user's data. We tested SCAN on three publicly available transcriptomes, each assembled using three assembly programs. Moreover, we sequenced the transcriptome of the oomycete Achlya hypogyna and compared de novo assemblies from Velvet, ABySS, and the CLC Genomics Workbench assembly algorithms. One thousand one hundred twenty-eight of the CLC transcripts were statistically similar to the reference, compared with 49 of the Velvet transcripts and 937 of the ABySS transcripts. SCAN's strength is providing statistical support for transcript assemblies in a biological context. However, SCAN is designed to compare distinct node sets in networks, therefore it can also easily be extended to perform statistical comparisons on any network graph regardless of what the nodes represent.
ISSN: 0737-4038

hal-01544800
https://hal.archives-ouvertes.fr/hal-01544800
DOI : 10.1093/molbev/mst087

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Evolution involves interplay between natural selection and developmental constraints(1-3). This is seen, for example, when digits are lost from the limbs during evolution(1,3,4). Extant archosaurs (crocodiles and birds) show several instances of digit loss(3,5,6) under different selective regimes, and show limbs with one, two, three, four or the ancestral number of five digits. The `lost' digits sometimes persist for millions of years as developmental vestiges(7-10). Here we examine digit loss in the Nile crocodile and five birds, using markers of three successive stages of digit development. In two independent lineages under different selection, wing digit I and all its markers disappear. In contrast, hindlimb digit V persists in all species sampled, both as cartilage, and as Sox9-expressing precartilage domains, 250 million years after the adult digit disappeared. There is therefore a mismatch between evolution of the embryonic and adult phenotypes. All limbs, regardless of digit number, showed similar expression of sonic hedgehog (Shh). Even in the one-fingered emu wing, expression of posterior genes Hoxd11 and Hoxd12 was conserved, whereas expression of anterior genes Gli3 and Alx4 was not. We suggest that the persistence of digit V in the embryo may reflect constraints, particularly the conserved posterior gene networks associated with the zone of polarizing activity (ZPA(11)). The more rapid and complete disappearance of digit I may reflect its ZPA-independent specification, and hence, weaker developmental constraints. Interacting with these constraints are selection pressures for limb functions such as flying and perching. This model may help to explain the diverse patterns of digit loss in tetrapods. Our study may also help to understand how selection on adults leads to changes in development.
ISSN: 0028-0836

hal-01545485
https://hal.archives-ouvertes.fr/hal-01545485
DOI : 10.1038/nature12336

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Primary hepatocyte cultures are now considered as convenient models for in vitro analyzing liver drug transport. However, if primary human and rat hepatocytes have been well-characterized with respect to drug transporter expression and regulation, much less is known for primary mouse hepatocytes. The present study was therefore designed to gain insights about this point. The profile of sinusoidal and canalicular drug transporter mRNA expression in short time (4h)-cultured mouse hepatocytes was found to be highly correlated with that of freshly isolated hepatocytes; by contrast, those of counterparts cultured for a longer time (until 4days) either in monolayer configurations on plastic or collagen or in sandwich configuration with matrigel were profoundly altered: uptake drug transporters such as Oct1, Oatps and Oat2 were thus down-regulated, whereas most of efflux transporters such as Mdr1a/b, Mrp3, Mrp4 and Bcrp were induced. Moreover, short time-cultured hepatocytes exhibited the highest levels of sinusoidal influx transporter activities. Transporter-mediated drug secretion into canalicular networks was however only observed in sandwich-cultured hepatocytes. Mouse hepatocytes cultured either in monolayer or sandwich configurations were finally shown to exhibit up-regulation of referent transporters in response to exposure to prototypical activators of the drug sensing receptors pregnane X receptor, aryl hydrocarbon receptor or constitutive androstane receptor. Taken together, these data demonstrate the feasibility of using primary mouse hepatocytes for investigating potential interactions of xenobiotics with hepatic transporter activity or regulation, provided that adequate culture conditions are retained.
ISSN: 0928-0987

inserm-00823243
http://www.hal.inserm.fr/inserm-00823243
DOI : 10.1016/j.ejps.2013.01.013
PUBMED : 23396053

Éditeur(s) : HAL CCSD
Résumé : International audience
The SOX8 and SOX9 transcription factors are involved in, among others, sex differentiation, male gonad development and adult maintenance of spermatogenesis. Sox8(-/-) mice lacking Sox9 in Sertoli cells fail to form testis cords and cannot establish spermatogenesis. Although genetic and histological data show an important role for these transcription factors in regulating spermatogenesis, it is not clear which genes depend upon them at a genome-wide level. To identify transcripts that respond to the absence of Sox8 in all cells and Sox9 in Sertoli cells we measured mRNA concentrations in testicular samples from mice at 0, 6 and 18 days post-partum. In total, 621 and 629 transcripts were found at decreased or increased levels, respectively, at different time points in the mutant as compared to the control samples. These mRNAs were categorized as preferentially expressed in Sertoli cells or germ cells using data obtained with male and female gonad samples and enriched testicular cell populations. Five candidate genes were validated at the protein level. Furthermore, we identified putative direct SOX8 and SOX9 target genes by integrating predicted SOX-binding sites present in potential regulatory regions upstream of the transcription start site. Finally, we used protein network data to gain insight into the effects on regulatory interactions that occur when Sox8 and Sox9 are absent in developing Sertoli cells. The integration of testicular samples with enriched Sertoli cells, germ cells and female gonads enabled us to broadly distinguish transcripts directly affected in Sertoli cells from others that respond to secondary events in testicular cell types. Thus, combined RNA profiling signals, motif predictions and network data identified putative SOX8/SOX9 target genes in Sertoli cells and yielded insight into regulatory interactions that depend upon these transcription factors. In addition, our results will facilitate the interpretation of genome-wide in vivo SOX8 and SOX9 DNA binding data.
Andrology

hal-00877013
https://hal.archives-ouvertes.fr/hal-00877013
DOI : 10.1111/j.2047-2927.2012.00049.x
PUBMED : 23315995

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
High sea surface temperature accompanied by high levels of solar irradiance is responsible for the disruption of the symbiosis between cnidarians and their symbiotic dinoflagellates from the genus Symbiodinium. This phenomenon, known as coral bleaching, is one of the major threats affecting coral reefs around the world. Because an important molecular trigger to bleaching appears related to the production of reactive oxygen species (ROS), it is critical to understand the function of the antioxidant network of Symbiodinium species. In this study we investigated the response of two Symbiodinium species, from contrasting environments, to a chemically induced oxidative stress. ROS produced during this oxidative burst reduced photosynthesis by 30 to 50% and significantly decreased the activity of superoxide dismutase. Lipid peroxidation levels and carotenoid concentrations, especially diatoxanthin, confirm that these molecules act as antioxidants and contribute to the stabilization of membrane lipids. The comparative analysis between the two Symbiodinium species allowed us to highlight that Symbiodinium sp. clade A temperate was more tolerant to oxidative stress than the tropical S. kawagutii clade F. These differences are very likely a consequence of adaptation to their natural environment, with the temperate species experiencing conditions of temperature and irradiance much more variable and extreme.
ISSN: 0140-7791

hal-01546161
https://hal.archives-ouvertes.fr/hal-01546161
DOI : 10.1111/pce.12825

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Molecular diagnosis of congenital toxoplasmosis or disseminated toxoplasmosis is based mainly on PCR. The repeated DNA element rep529 has become the main DNA target used in most PCR methods, whether laboratory developed or commercial. In this multicenter study, we evaluated the Toxoplasma ELITe MGB (Elitech) commercial kit by comparison with three reference quantitative PCR assays (RAs) used routinely in three proficient laboratories of the French National Reference Center for Toxoplasmosis network, using Toxoplasma calibrated suspensions diluted to obtain a range of concentrations from 0.1 to 10,000 parasites/ml. These suspensions were extracted with either the DNA extraction kit (EXTRAblood; Elitech) recommended by the manufacturer or the QIAamp DNA minikit (Qiagen). The Toxoplasma ELITe MGB assay was also evaluated on a panel of 128 clinical samples, including 56 amniotic fluid samples, 55 placenta samples, and various other samples, of which 95 originated from patients with proven toxoplasmosis. The ELITe MGB assay amplified low-concentration replicates (<10 parasites/ml) of calibrated suspensions less frequently than the RAs of 2/3 laboratories. Additionally, the combination of EXTRAblood and Toxoplasma ELITe MGB yielded poorer sensitivity than the combination of QIAamp DNA minikit and ELITe MGB for low parasite concentrations (P < 0.001 for 1 parasite/ml). On clinical samples, the sensitivity and the specificity of the commercial assay were 89% and 100%, respectively. The sensitivity ranged from 79% (placenta samples) to 100% (amniotic fluid samples). Overall, this study shows that the Toxoplasma ELITe MGB assay is suitable for the diagnosis of toxoplasmosis from non-cell-rich or non-hemoglobin-rich samples and that the EXTRAblood kit is not optimal.
ISSN: 0095-1137

hal-01526432
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432/file/Evaluation%20of%20the%20Toxoplasma.pdf
DOI : 10.1128/JCM.02379-16

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : Intraguild predation (IGP) is a type of biological interaction involving the killing and consuming of competing species that exploit similar and often limited resources. This phenomenon is widespread among a great variety of taxonomic groups and has already been reported for mosquito (Diptera: Culicidae) larvae. Moreover, the larvae of certain mosquito species of the tribe Sabethini have evolved modified mouthparts ending in rigid apical structures signaling their capacity to be effective intraguild predators. We assumed that IGP confers a selective advantage under severe competitive conditions by both providing an immediate energetic gain and reducing potential competition. Because potential competition is likely to increase with decreasing habitat size, we hypothesized that the proportion of species with modified mouthparts would increase in smaller aquatic habitats. We tested this hypothesis by examining the mosquito species naturally associated with phytotelmata of decreasing sizes in French Guiana. We show that the degree of specialization in mosquito-phytotelm associations is high, suggesting a long coevolutive process. Indeed, short-term interaction experiments confirmed that species with modified mouthparts are able to prey upon similarly-sized intraguild prey and are, thus, effective intraguild predators. In addition, these species are larger and associated with smaller phytotelmata than those with typical mouthparts. Moreover, below a certain threshold of phytotelm size, only species with modified mouthparts were present. These results show that IGP confers a selective advantage under severe competitive conditions and results from the coadaptation of mosquito species to their specific phytotelm habitat. The presence of functionally analogous structures in different mosquito genera also implies that IGP has emerged from convergent evolution in small phytotelmata.
ISSN: 0269-7653

hal-01603304
https://hal.archives-ouvertes.fr/hal-01603304
DOI : 10.1007/s10682-016-9862-3
PRODINRA : 405771

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Clin Microbiol Infect 2012; 18 (Suppl. 4): 4043 Abstract In order to study complex microbial communities and their associated mobile genetic elements, such as the human gut microbiome, evolutionists could explore their genetic diversity with shared sequence networks. In particular, the detection of remarkable structures in gene networks of the gut microbiome could serve to identify important functions within the community, and would ease comparison of data sets from microbiomes of various sources (human, ape, mouse etc.) in a single analysis.
ISSN: 1198-743X

hal-01544804
https://hal.archives-ouvertes.fr/hal-01544804
DOI : 10.1111/j.1469-0691.2012.03856.x

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definite diagnosis relies on parasite DNA detection, but the incidence and burden of disease are ill-known in HIV-negative patients. A three-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, to record the frequency of Toxoplasma DNA detection in ICPs, to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, out of 31,640 PCR performed in ICPs, 610 were positive (323 patients). Blood (n=337), cerebrospinal fluid (n=101) and aqueous humor (n=100) samples were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem-cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV+; the remaining 62% consisted in 72 HSCT, 14 solid-organ transplants, and 26 miscellaneous immunodeficiencies. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and received specific treatment. Overall survival of allo-HSCT patients at two months was better in centers with PCR follow-up than in other centers (p<0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide pre-emptive treatment and improve outcome.
ISSN: 0095-1137

hal-01134189
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134189
DOI : 10.1128/JCM.03282-14
PUBMED : 25762774

Éditeur(s) : HAL CCSD
Résumé : International audience
Symbiosis is a widespread phenomenon in the biosphere. In marine benthic environments breakdown of symbiosis is responsible for coral bleaching and dramatically affects coral reef ecosystems functioning [1]. In the water column, planktonic organisms are key component of pelagic ecosystems and a number of species form mutualistic association with microalgae forming a photosymbiosis [2]. Here we intended to investigate the genetic basis of photosymbiosis, through a transcriptomic approach on marine plankton organisms. We focused more specifically on associations occurring between radiolarian host (protist, zooplankton) and dinoflagellates symbiont (protist, phytoplankton) living inside the host cell. It has recently been highlighted that these holobionts are widespread in oligotrophic open oceans and there are also evidences of their fundamental implication in biogeochemical carbon, silica and strontium cycles [3, 4, 5, 6]. RNA-seq technologies allow obtaining an unprecedented amount of data for unicellular organisms isolated from the environment [7]. The study of such non-model holobionts datasets requires de novo assembly, which implies considerable computational resources and the potential production of chimeric sequences [8, 9].We therefore developed an original strategy aiming at accelerating and improving de novo assembly for holobiont datasets. We chose SIMKA [10] a fast kmer-based method initially developed to estimate the similarity between numerous metagenomic datasets, and which has been recently adapted to extract their common sequences. As our symbionts are identified, we used SIMKA to compare our holobionts transcriptomes to publicly available dinoflagellates transcriptomes [11] generating two datasets, one composed of reads from the symbionts and another with reads from the host (for which no reference data are currently available). Independent assemblies were then performed in parallel, accelerating the study process, and minimizing the proportion of resulting chimeric sequences. Our strategy produced a unique and comprehensive genomic dataset for Radiolaria [12, 13], and offers a pragmatic, large scale, comparison strategy to assemble and study holobionts [9]. Our new sequences obtained from holobionts study will be used for phylogenomics investigation, as reference for environmental metagenomic studies and ultimately to understand and characterize the molecular basis of symbiotic relationships in the plankton.Bibliografic references :[1] Simon K. Davy, Denis Allemand, and Virginia M. Weis. “Cell Biology of Cnidarian-Dinoflagellate Symbiosis”. In: Microbiology and Molecular Biology Reviews 76.2 (June 1, 2012), pp. 229–261. issn: 1092-2172, 1098- 5557. doi: 10.1128/MMBR.05014-11.[2] Janouškovec, J. et al. “Major transitions in dinoflagellate evolution unveiled by phylotranscriptomics”. in: PNAS 201614842 (2016). doi:10.1073/pnas.1614842114[3] Tristan Biard et al. “In situ imaging reveals the biomass of giant protists in the global ocean”. In: Nature advance online publication (Apr. 20, 2016). issn: 0028-0836. doi: 10.1038/nature17652.[4] Lionel Guidi et al. “Plankton networks driving carbon export in the olig- otrophic ocean”. In: Nature 532.7600 (Apr. 28, 2016), pp. 465–470. issn: 0028-0836. doi: 10.1038/nature16942.[5] Diane K. Stoecker et al. “Acquired phototrophy in aquatic protists”. In: Aquatic Microbial Ecology 57.3 (Nov. 24, 2009), pp. 279–310. doi: 10.3354/ame01340.[6] Johan Decelle et al. “An original mode of symbiosis in open ocean plankton”. In: Proceedings of the National Academy of Sciences 109.44 (Oct. 30, 2012), pp. 18000–18005. issn: 0027-8424, 1091-6490. doi: 10. 1073/pnas.1212303109.[7] Sergio Balzano et al. “Transcriptome analyses to investigate symbiotic relationships between marine protists”. In: Frontiers in Microbiology 6 (Mar. 17, 2015). issn: 1664-302X. doi: 10.3389/fmicb.2015.00098.[8] Li, B. et al. “Evaluation of de novo transcriptome assemblies from RNA-Seq data”. In: Genome Biology 15, 553 (2014).[9] Sangwan, N., Xia, F. & Gilbert, J. A. “Recovering complete and draft population genomes from metagenome datasets”. In: Microbiome 4, 8 (2016).[10] Gaëtan Benoit et al. “Multiple comparative metagenomics using mul- tiset k -mer counting”. In: PeerJ Computer Science 2 (Nov. 14, 2016). doi: 10.7717/peerj-cs.94.[11] Patrick J. Keeling et al. “The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing”. In: PLOS Biol 12.6 (June 2014), e1001889. issn: 1545-7885. doi: 10.1371/journal.pbio.1001889.[12] Burki, F. et al. “Evolution of Rhizaria: new insights from phylogenomic analysis of uncultured protists”. In BMC Evolutionary Biology 10, 377 (2010).
International Conference on Holobionts
Paris, France

hal-01575069
https://hal.inria.fr/hal-01575069

Éditeur(s) : HAL CCSD
Résumé : contient des versions PDF d'articles scientifiques (versions éditeur)
Spectrins are actin binding proteins that constitute the main components of membrane skeletons, the protein network located under the plasma membrane. Erythroid or non erythroid (in this case, they are called fodrins), spectrins play an important structural function in the membrane as demonstrated in the red blood cell. Spectrins are composed of two long α and β chains, associated in tetramers (αβ)2, forming the long flexible filaments of the network. Both chains are composed of repeating units which are folded in a triple helical arrangement (A, B and C helices), except for segment α10 which corresponds to a Src Homology 3 domain (SH3). The head-to-head interaction between dimers implies the N-terminal end of α chain and the C-terminal end of β chain. A model was proposed for the tetramerization site of spectrin : the two A and B helices of the last repeat of α chain interact with the C helix of the β chain in order to constitute a triple-helical structure similar to the repeats along the remainder of spectrin molecule. This model was first inferred from the relationship between the severity of the spectrin self-association defect and the location of the underlying mutations found in hereditary elliptocytosis (HE). Using recombinant peptides we defined the region, on both chains, which was sufficient and necessary to generate a fully functional tetramerization site. Producing peptides carrying a βHE mutation, we reproduced the tetramerization defect as observed in red blood cells of patients.
Finally, the presence of an SH3 domain probably gives to spectrins new functions which are different from the stability of the membrane. After contesting the existence of interaction between the fodrin SH3 domain and the α subunit of epithelial sodium channel sensitive to amiloride, we searched for partners of this domain, by screening a rat kidney library with the yeast two-hybrid system. We identified severals proteins implicated in the actin polymerization asoociated with motility or cell differenciation, suggesting that SH3 domain could play a part in this process.
Les spectrines, protéines liant l'actine, sont des constituants majeurs du squelette membranaire, réseau multiprotéique localisé sous la membrane plasmique. Érythroïdes ou non érythroïdes (dans ce cas, on les appelle fodrines), les spectrines ont un rôle structural important dans la membrane comme cela a déjà été démontré, pour la spectrine, dans le globule rouge. Elles sont constituées de deux longues chaînes a et ß associées côte à côte en tétramères (aß)2 qui forment les longs filaments du réseau. Chacune des chaînes est composée par la répétition de segments homologues, 22 pour a et 17 pour ß. Ces segments sont constitués de trois hélices a (hélices A, B et C) repliées sur elles-mêmes. Cette succession de structures trihélicoïdales est parfois interrompue par un domaine particulier comme le domaine SH3 (Src Homology 3) présent au milieu de la chaîne a. Les tétramères (aß)2 de spectrine constituent les filaments du squelette membranaire. L'interaction tête-à-tête de deux dimères aß implique les extrémités NH2 de la chaîne a et COOH de la chaîne ß. D'une part la sévérité du défaut d'auto-association et la localisation des mutations associées à celui-ci et d'autre part, les séquences en acides aminés des extrémités impliquées dans le site d'auto-association ont permis de proposer un modèle : la première hélice C isolée de la chaîne a pourrait s'associer aux deux dernières hélices A et B de la chaîne ß pour reconstituer une unité conformationnelle trihélicoïdale semblable à celles observées le long de la molécule. Un défaut dans la formation du tétramère est le support moléculaire le plus fréquemment observé dans les elliptocytoses héréditaires (HE). À l'aide de peptides recombinants, nous avons défini, sur les deux chaînes, les régions nécessaires et suffisantes possédant les caractéristiques pleinement fonctionnelles du site de tétramérisation. Nous avons ensuite, par mutagenèse dirigée, reproduit le lien entre la présence de mutations HE localisées dans les hélices A ou B et le défaut d'auto-association observé dans les globules rouges de patients HE. La présence d'un domaine SH3 localisé au milieu de la chaîne a confère probablement aux spectrine des fonctions autres que le maintien et la stabilité de la membrane. Les SH3, petits domaines protéiques, participent aux interactions protéine/protéine. Le seul partenaire connu du domaine SH3 de la fodrine était la sous-unité a du canal sodium sensible à l'amiloride (ENaC) mais la fonction de ce complexe n'était pas encore caractérisée. À l'aide de différentes méthodes, nous avons remis en cause l'interaction directe entre ENaC et le SH3 de la fodrine. La fonction de ce domaine SH3 étant liée à la nature de son ligand, nous avons donc recherché les partenaires putatifs du domaine SH3 de la fodrine par la technique du double-hybride. 29 partenaires ont été identifiés, regroupés en 19 familles et 10 clones isolés. La spécificité des interactions a été étudiée à la fois par double-hybride, à l'aide de mutants du domaine SH3 de la fodrine produits par mutagenèse dirigée. Les interactions vis-à-vis d'autres domaines SH3 (spectrine ou une protéine de levure non relatée Scd2) ont été également analysées. Enfin, la spécificité de certains partenaires a été confirmée par des études d'interactions in vitro. Deux des protéines les plus spécifiques du domaine SH3 de la fodrine sont des protéines tyrosine-phosphatase PTP. La première est l'isoforme A de PTP de faible poids moléculaire (LMPTPA) mais l'interaction n'a pas été confirmée in vitro. La deuxième, TD14, est une nouvelle PTP dont la seule fonction connue est d'inhiber la formation des foyers tumoraux des cellules surexprimant l'oncogène Ha-ras. Ces PTP pourraient soit déphosphoryler la fodrine, soit être recrutées sous la membrane pour déphosphoryler une autre cible. Nous avons également identifié trois partenaires (N-WASP, Evl et une protéine de la famille des formines) suggérant que les domaines SH3 des spectrines pourraient être impliqués dans les processus de polymérisation de l'actine liés à la mobilité ou la différenciation cellulaire. Mot clés : spectrine, fodrine, tétramérisation, SH3, double-hybride, polymérisation de l'actine
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tel-00284819
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