Éditeur(s) : Springer
Résumé : Pearl oysters belonging to the genus Pinctada (Bivalvia: Pteriidae) are widely distributed between the Indo-Pacific and western Atlantic. The existence of both widely distributed and more restricted species makes this group a suitable model to study diversification patterns and prevailing modes of speciation. Phylogenies of eight out of the 11 currently recognised Pinctada species using mitochondrial (cox1) and nuclear (18S rRNA) data yielded two monophyletic groups that correspond to shell size and presence/absence of hinge teeth. Character trace of these morphological characters onto the molecular phylogeny revealed a strong correlation. Pinctada margaritifera appears polyphyletic with specimens from Mauritius grouping in a different clade from others of the French Polynesia and Japan. Hence, P. margaritifera might represent a species complex, and specimens from Mauritius could represent a different species. Regarding the putative species complex Pinctada fucata/Pinctada martensii/Pinctada radiata/Pinctada imbricata, our molecular analyses question the taxonomic validity of the morphological characters used to discriminate P. fucata and P. martensii that exhibited the lowest genetic divergence and are most likely conspecific as they clustered together. P. radiata and P. imbricata were recovered as monophyletic. The absence of overlapping distributions between sister lineages and the observed isolation by distance suggests that allopatry is the prevailing speciation mode in Pinctada. Bayesian dating analysis indicated a Miocene origin for the genus, which is consistent with the fossil record. The northward movement of the Australian plate throughout the Miocene played an important role in the diversification process within Pinctada.
Marine Biotechnology (1436-2228) (Springer), 2011-04 , Vol. 13 , N. 2 , P. 181-192

Droits : Springer Science+Business Media, LLC 2010
http://archimer.ifremer.fr/doc/00035/14635/14015.pdf
DOI:10.1007/s10126-010-9278-y
http://archimer.ifremer.fr/doc/00035/14635/

Éditeur(s) : HAL CCSD
Résumé : Gravitropism is a major process in vertical growth as it allows the positioning of plant in the gravity field and thus, for trees, it takes part in the light foraging strategies. Without any gravitropism, trees would adopt a weeping habit or fall on the ground due to the increasing with growth supported weight, especially at the advance regeneration stage (sapling stage) in the understorey, where tree are very slender and poorly stiff. Most of the gravitropic studies are made by physiologists in order to understand the process and thus are associated to complex laboratory methods (genetic engineering, anatomical studies, accurate 2D ou 3D measurements of form changes with time). In order to study the ecological relevance and the specific diversity of gravitropic performances in natural forests, we developed a framework that uses different kinds of datas. Synchronical analysis has been done i) at the population level in large sample of trees and ii) at the tree level from destructive measurement of the dissymmetry maturation strains known to be the main motor of the posture control reaction of trees. In both cases, biomechanical models allows to estimate some aspects of the dynamic gravitropic process. Diachronical analysis has been done in natural conditions on permanent plots, or in a more traditional way, by observing in greenhouse experiments the righting movements of plants artificially tilted. In the first case, the problem is the high variability of natural disturbances and the slowness of growth and movements in the dark understorey. The second choice allows a measurement of a capacity (i.e. the ability of the species to react in quite extreme conditions of verticality disturbance but good for growth light and nutrient conditions) that is more easy to analyse, but is maybe not so relevant for estimating the ecological strategy (some species could have developed a high efficience of gravitropic reaction in natural conditions by avoiding the mechanical disturbance or adapting the reaction to slow growth and changing environments in natural conditions). All approaches use the same basic biomechanical modelling, i) to analyse simultaneously the reaction and the disturbance (due to the weight increase) during growth, or ii) to combine different parameters (geometry, growth, weight, maturation strains) involved in shape changes and posture control. They give a classification of the species according to their gravitropic performances. Results on 15 species are discussed, with relation to shade-tolerance or avoidance.
6th Plant Biomechanics Conference
Cayenne, France

hal-00565956
https://hal.archives-ouvertes.fr/hal-00565956

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p=0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.
ISSN: 1079-9796

hal-01668332
https://hal.univ-antilles.fr/hal-01668332
DOI : 10.1016/j.bcmd.2016.02.006

Éditeur(s) : HAL CCSD SPRINGER
Résumé : International audience
A key question in evolutionary biology is the reproducibility of adaptation. This question can now be quantitatively analyzed using experimental evolution coupled to whole genome sequencing (WGS). With complete sequence data, one can assess convergence among replicate populations. In turn, convergence reflects the action of natural selection and also the breadth of the field of possible adaptive solutions. That is, it provides insight into how many genetic solutions or adaptive paths may lead to adaptation in a given environment. Convergence is both a property of an adaptive landscape and, reciprocally, a tool to study that landscape. In this chapter we present the links between convergence and the properties of adaptive landscapes with respect to two types of microbial experimental evolution. The first tries to reconstruct a full adaptive landscape using a handful of carefully identified mutations (the reductionist approach), while the second uses WGS of replicate experiments to infer properties of the adaptive landscape. Reductionist approaches have highlighted the importance of epistasis in shaping the adaptive landscape, but have also uncovered a wide diversity of landscape architectures. The WGS approach has uncovered a very high diversity of beneficial mutations that affect a limited set of genes or functions and also suggests some shortcomings of the reductionist approach. We conclude that convergence may be better defined at an integrated level, such as the genic level or even at a phenotypic level, and that integrated mechanistic models derived from systems biology may offer an interesting perspective for the analysis of convergence at all levels.
ECOLOGICAL GENOMICS: ECOLOGY AND THE EVOLUTION OF GENES AND GENOMES

ISBN : 978-94-007-7347-9; 978-94-007-7346-2
hal-01544757
https://hal.archives-ouvertes.fr/hal-01544757
DOI : 10.1007/978-94-007-7347-9__11

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper investigates the narrative challenges and opportunities that contemporary virology offers to popular science and to fiction. The study of viruses reveals extremely complex relations, playing out over different physical and temporal scales. Viruses constitute a heterogeneous population whose interactions with living organisms occur on multiple levels, and whose numbers are vastly superior to human and even bacterial populations on earth. The resulting challenges for narration can be grouped into three main formal questions. The first is the problem of scale, since the numbers and sizes of virus and host populations are vastly different, as are the temporalities over which they transform and survive. The second is the complexity of actants, since viruses are involved in relations where destruction and mutual benefit can overlap, and genetic transformations are played out over many generations. The third is the choice of images through which to convey their behaviours: many existing metaphors in microbiology, such as “chimeras”, “parasites” or “kill-the-winner dynamics”, carry the narrative potential of a mythological and/or theatrical imagination.These questions will first be examined as challenges encountered in the narration of biology for vulgarization purposes, and effects on narrative forms will be outlined: shifts in focalization in order to create multiscalar perspectives; unstable actantial models as expressions of complex relations; and the use or resistance to narrative structures implied by several key metaphors in virological discourse. These formal characteristics will then be presented through two case studies drawn from contemporary fiction. In his “scientific fable” Conflits Intérieurs (2015), microbiologist Eric Bapteste creates a multiscalar narrative by using humans and viruses as both protagonists and narrators in a battle of ideas. In the graphic novel aâma (2011-2014), Frederik Peeters explores the ambiguous potential, both symbiotic and threatening, of a meta-organism uniting humans with microscopic agents. Both these novels play with scale, metaphor and actants so as to question the fundaments of human identity. They posit the act of narration as a defining human attribute, and consequently use the narrative voice as an arena in which we observe the weakening of the notion of the subject by microbiology.
“Narrative, Cognition & Science” Symposium
Erlangen, Germany

hal-01434744
https://hal.archives-ouvertes.fr/hal-01434744

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : International audience
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells, which promote inflammation and induce hepatocyte death, mediated by the activated invariant natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the spleen, thymus, and bone marrow in Parp2-deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis. We show that 1) the genetic inactivation of Parp2, but not Parp1, protected mice from ConA hepatitis without deregulating cytokine expression and leucocyte recruitment; 2) cellularity was lower in the thymus, but not in spleen, liver, or bone marrow of Parp2-/- mice; 3) spleen and liver iNKT lymphocytes, as well as thymic T and NKT lymphocytes were reduced in Parp2 knockout mice. In conclusion, our results suggest that the defect of T-lymphocyte maturation in Parp2 knockout mice leads to a systemic reduction of iNKT cells, reducing hepatocyte death during ConA-mediated liver damage, thus protecting the mice from hepatitis.NEW & NOTEWORTHY The genetic inactivation of Parp2, but not Parp1, protects mice from concanavalin A hepatitis. Immune cell populations are lower in the thymus, but not in the spleen, liver, or bone marrow of Parp2-deficient mice compared with wild-type mice. Spleen and liver invariant natural killer T (NKT) lymphocytes, as well as thymic T and NKT lymphocytes, are reduced in Parp2-deficient mice
ISSN: 0193-1857

hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01630440/file/102513_1_merged_1499199857-1.pdf
DOI : 10.1152/ajpgi.00436.2016

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background & Aims: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of pathogen associated molecular patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis. Methods: Hepatitis was induced in mice by independent injections of two different bacterial PAMPs: lipopolysaccharide (LPS) and unmethylated CpG oligodeoxynucleotide (CpG-DNA) motifs. The role of RIPK1 was evaluated by using mice specifically lacking RIPK1 in liver parenchymal cells (Ripk1(LPC-KO)). Administration of liposome-encapsulated clodronate served to investigate the role of Kupffer cells in the establishment of the disease. Etanercept, a tumor necrosis factor (TNF)-decoy receptor, was used to study the contribution of TNF-alpha during LPS-mediated liver injury. Results: Whereas RIPK1 deficiency in liver parenchymal cells did not trigger basal hepatolysis, it greatly sensitized hepatocytes to apoptosis and liver damage following a single injection of LPS or CpG-DNA. Importantly, hepatocyte death was prevented by previous macrophage depletion or by TNF inhibition. Conclusions: Our data highlight the pivotal function of RIPK1 in maintaining liver homeostasis in conditions of macrophage-induced TNF burst in response to PAMPs sensing. Lay summary: Excessive death of hepatocytes is a characteristic of liver injury. A new programmed cell death pathway has been described involving upstream death ligands such as TNF and downstream kinases such as RIPK1. Here, we show that in the presence of LPS liver induced hepatic injury was due to secretion of TNF by liver macrophages, and that RIPK1 acts as a powerful protector of hepatocyte death. This newly identified pathway in the liver may be helpful in the management of patients to predict their risk of developing acute liver failure. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
ISSN: 0168-8278

hal-01532060
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01532060
DOI : 10.1016/j.jhep.2017.01.005
PUBMED : 28088582

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Defining homologous genes is important in many evolutionary studies but raises obvious issues. Some of these issues are conceptual and stem from our assumptions of how a gene evolves, others are practical, and depend on the algorithmic decisions implemented in existing software. Therefore, to make progress in the study of homology, both ontological and epistemological questions must be considered. In particular, defining homologous genes cannot be solely addressed under the classic assumptions of strong tree thinking, according to which genes evolve in a strictly tree-like fashion of vertical descent and divergence and the problems of homology detection are primarily methodological. Gene homology could also be considered under a different perspective where genes evolve as ``public goods,'' subjected to various introgressive processes. In this latter case, defining homologous genes becomes a matter of designing models suited to the actual complexity of the data and how such complexity arises, rather than trying to fit genetic data to some a priori tree-like evolutionary model, a practice that inevitably results in the loss of much information. Here we show how important aspects of the problems raised by homology detection methods can be overcome when even more fundamental roots of these problems are addressed by analyzing public goods thinking evolutionary processes through which genes have frequently originated. This kind of thinking acknowledges distinct types of homologs, characterized by distinct patterns, in phylogenetic and nonphylogenetic unrooted or multirooted networks. In addition, we define `` family resemblances'' to include genes that are related through intermediate relatives, thereby placing notions of homology in the broader context of evolutionary relationships. We conclude by presenting some payoffs of adopting such a pluralistic account of homology and family relationship, which expands the scope of evolutionary analyses beyond the traditional, yet relatively narrow focus allowed by a strong tree-thinking view on gene evolution.
ISSN: 0737-4038

hal-01544794
https://hal.archives-ouvertes.fr/hal-01544794
DOI : 10.1093/molbev/mst228

Éditeur(s) : HAL CCSD
Résumé :  
Improvement of wood quality related traits is currently hampered by costly chemical and technological assays and the necessity to wait until the trees are nearly mature to evaluate wood properties. The availability of a vast quantity of genomic data opens now a new avenue to identify early selection criteria based on molecular information and therefore increase selection efficiency. Association mapping is becoming a method of choice to identify QTN (quantitative trait nucleotide) that contribute to complex trait variation. The implementation of this approach requires on the one hand knowledge of the molecular mechanisms underlying trait variation and polymorphism within candidate genes, and on the other hand the availability of phenotypically well characterized genetic material. We are developing this strategy in the frame of the French maritime pine breeding program, an economically important forest tree species in the South Western Europe. About 500 trees from the breeding population were evaluated for wood physical and chemical properties through the analysis of 2,800 half-sib progenies and 1,500 clones in 8 field tests. These same trees are being genotyped at 185 SNPs obtained from the sequencing of 41 candidate genes, and an additional set of 200 eSNPs detected in 147 EST-contigs (to be used as control). Statistical association between the breeding values of the 500 trees and their respective genotypes will be tested using mixed models accounting for relatedness among individuals of the breeding population.
IUFRO-CTIA joint conference, "Adaptation, Breeding and Conservation in the Era of Forest Tree Genomics and Environmental Change"
Québec City, Canada

hal-01032075
https://hal.archives-ouvertes.fr/hal-01032075

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Transposable elements are major constituents of eukaryote genomes and have a great impact on genome structure and stability. They can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution among several genomes is an essential condition to study their dynamics and to better understand their role in species evolution. LTR-retrotransposons have been reported in many diverse eukaryote species, describing a ubiquitous distribution. Given their abundance, diversity and their extended ranges in C-values, environment and life styles, crustaceans are a great taxon to investigate the genomic component of adaptation and its possible relationships with TEs. However, crustaceans have been greatly underrepresented in transposable element studies. Using both degenerate PCR and in silico approaches, we have identified 35 Copia and 46 Gypsy families in 15 and 18 crustacean species, respectively. In particular, we characterized several full-length elements from the shrimp Rimicaris exoculata that is listed as a model organism from hydrothermal vents. Phylogenic analyses show that Copia and Gypsy retrotransposons likely present two opposite dynamics within crustaceans. The Gypsy elements appear relatively frequent and diverse whereas Copia are much more homogeneous, as 29 of them belong to the single GalEa clade, and species-or lineage-dependent. Our results also support the hypothesis of the Copia retrotransposon scarcity in metazoans compared to Gypsy elements. In such a context, the GalEa-like elements present an outstanding wide distribution among eukaryotes, from fishes to red algae, and can be even highly predominant within a large taxon, such as Malacostraca. Their distribution among crustaceans suggests a dynamics that follows a ``domino days spreading'' branching process in which successive amplifications may interact positively.
ISSN: 1932-6203

hal-01544761
https://hal.archives-ouvertes.fr/hal-01544761
DOI : 10.1371/journal.pone.0057675

Éditeur(s) : HAL CCSD Embrapa Amazônia Oriental
Résumé :  
absent
Modelling and experimental research on genetic processes in tropical and temperate forests [proceedings]
Kourou, Guyane, France

hal-01032053
https://hal.archives-ouvertes.fr/hal-01032053

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The Chile Triple junction is a natural laboratory to study the interactions between magmatism and tectonics during the subduction of an active spreading ridge beneath a continent. The MLBA plateau (Meseta del Lago Buenos Aires) is one of the Neogene alkali basaltic plateaus located in the back-arc region of the Andean Cordillera at the latitude of the current Chile Triple junction. The genesis of MLBA can be related with successive opening of slabs windows beneath Patagonia: within the subducting Nazca Plate itself and between the Nazca and Antarctic plates. Detailed Ar-40/Ar-39 dating and geochemical analysis of bimodal magmatism from the western flank of the MLBA show major changes in the back-arc magmatism. which occurred between 14.5 Ma and 12.5 Ma with the transition from calc-alkaline lavas (Cerro Plomo) to alkaline lavas (MLBA) in relation with slab window opening. In a second step, at 4-3 Ma, alkaline felsic intrusions were emplaced in the western flank of the MLBA coevally with the MLBA basalts with which they are genetically related. These late OIB-like alkaline to transitional basalts were generated by partial melting of the subslab asthenosphere of the subducting Nazca plate during the opening of the South Chile spreading ridge-related slab window. These basalts differentiated with small amounts of assimilation in shallow magma chambers emplaced along transtensional to extensional zones. The close association of bimodal magmatism with extensional tectonic features in the western MLBA is a strong support to the model of Patagonian collapse event proposed to have taken place between 5 and 3 Ma as a consequence of the presence of the asthenospheric window (SCR-1 segment of South Chile Ridge) below the MLBA area.
ISSN: 0377-0273

hal-00475648
https://hal.archives-ouvertes.fr/hal-00475648
DOI : 10.1016/j.jvolgeores.2009.11.022

Éditeur(s) : HAL CCSD Wiley
Résumé :  
Animals, especially insects, are principal pollen vectors of tropical trees and have behavior patterns that affect gene dispersal. Here, we explore complex pollination systems using a new simulation model Eco-Gene and considering, among other factors, flowering synchrony, spatial distribution of trees, degree of selfing, population densities, pollinator flight distances, pollen deposition, and pollinator response to floral display size. Sensitivity analyses using two contrasting tree data sets (Jacaranda copaia and Dipteryx odorata) determined the importance of each parameter on three response variables: the proportion of seeds from self-pollination, effective population size, and pollen dispersal. Spatial considerations and attractiveness of floral displays were prominent features determining the population genetic result of pollinators, and some biological implications of the results are discussed.
ISSN: 0006-3606

hal-01032091
https://hal.archives-ouvertes.fr/hal-01032091
DOI : 10.1111/j.1744-7429.2004.tb00309.x

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Deciphering the evolutionary processes driving nucleotide variation in multiallelic genes is limited by the number of genetic systems in which such genes occur. The complementary sex determiner (csd) gene in the honey bee Apis mellifera is an informative example for studying allelic diversity and the underlying evolutionary forces in a well-described model of balancing selection. Acting as the primary signal of sex determination, diploid individuals heterozygous for csd develop into females, whereas csd homozygotes are diploid males that have zero fitness. Examining 77 of the functional heterozygous csd allele pairs, we established a combinatorical criteria that provide insights into the minimum number of amino acid differences among those pairs. Given a data set of 244 csd sequences, we show that the total number of csd alleles found in A. mellifera ranges from 53 (locally) to 87 (worldwide), which is much higher than was previously reported (20). Using a coupon-collector model, we extrapolate the presence of in total 116-145 csd alleles worldwide. The hypervariable region (HVR) is of particular importance in determining csd allele specificity, and we provide for this region evidence of high evolutionary rate for length differences exceeding those of microsatellites. The proportion of amino acids driven by positive selection and the rate of nonsynonymous substitutions in the HVR-flanking regions reach values close to 1 but differ with respect to the HVR length. Using a model of csd coalescence, we identified the high originating rate of csd specificities as a major evolutionary force, leading to an origin of a novel csd allele every 400,000 years. The csd polymorphism frequencies in natural populations indicate an excess of new mutations, whereas signs of ancestral transspecies polymorphism can still be detected. This study provides a comprehensive view of the enormous diversity and the evolutionary forces shaping a multiallelic gene.
ISSN: 0737-4038

hal-01544758
https://hal.archives-ouvertes.fr/hal-01544758
DOI : 10.1093/molbev/mst207

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The common endosymbiotic Wolbachia bacteria influence arthropod hosts in multiple ways. They are mostly recognized for their manipulations of host reproduction, yet, more recent studies demonstrate that Wolbachia also impact host behavior, metabolic pathways and immunity. Besides their biological and evolutionary roles Wolbachia are new potential biological control agents for pest and vector management. Importantly, Wolbachia-based control strategies require controlled symbiont transfer between host species and predictable outcomes of novel Wolbachia-host associations. Theoretically, this artificial horizontal transfer could inflict genetic changes within transferred Wolbachia populations. This could be facilitated through de novo mutations in the novel recipient host or changes of haplotype frequencies of polymorphic Wolbachia populations when transferred from donor to recipient hosts. Here we show that Wolbachia resident in the European cherry fruit fly, Rhagoletis cerasi, exhibit ancestral and cryptic sequence polymorphism in three symbiont genes, which are exposed upon microinjection into the new hosts Drosophila simulans and Ceratitis capitata. Our analyses of Wolbachia in microinjected D. simulans over 150 generations after microinjection uncovered infections with multiple Wolbachia strains in trans-infected lines that had previously been typed as single infections. This confirms the persistence of low-titer Wolbachia strains in microinjection experiments that had previously escaped standard detection techniques. Our study demonstrates that infections by multiple Wolbachia strains can shift in prevalence after artificial host transfer driven by either stochastic or selective processes. Trans-infection of Wolbachia can claim fitness costs in new hosts and we speculate that these costs may have driven the shifts of Wolbachia strains that we saw in our model system.
ISSN: 1932-6203

hal-01544765
https://hal.archives-ouvertes.fr/hal-01544765
DOI : 10.1371/journal.pone.0082402

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
A major requirement for malaria elimination is the development of transmission-blocking interventions. In vitro transmission-blocking bioassays currently mostly rely on the use of very few Plasmodium falciparum reference laboratory strains isolated decades ago. To fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of P. falciparum are suitable for in vitro transmission-blocking bioassays targeting functional maturity of male gametocytes: exflagellation. Plasmodium falciparum isolates were adapted to in vitro culture before being used for in vitro gametocyte production. Maturation was assessed by microscopic observation of gametocyte morphology over time of culture and the functional viability of male gametocytes was assessed by microscopic counting of exflagellating gametocytes. Suitability for in vitro exflagellation-blocking bioassays was determined using dihydroartemisinin and methylene blue. In vitro gametocyte production was achieved using two isolates from French Guiana and two isolates from Cambodia. Functional maturity of male gametocytes was assessed by exflagellation observations and all four isolates could be used in exflagellation-blocking bioassays with adequate response to methylene blue and dihydroartemisinin. This work shows that in vitro culture-adapted P. falciparum field isolates of different genetic background, from South America and Southeast Asia, can successfully be used for bioassays targeting the male gametocyte to gamete transition, exflagellation.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01182753
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753/file/LeBas%20et%202015%20version%20publie%20%281%29.pdf
DOI : 10.1186/s12936-015-0752-x

Éditeur(s) : HAL CCSD
Résumé : International audience
Spermatogenesis is a highly sophisticated process involved in the transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and the equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g., tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is divided into three phases. In the first the primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids. In the third the spermatids differentiate into spermatozoa in a process called spermiogenesis. Paracrine, autocrine, juxtacrine, and endocrine pathways all contribute to the regulation of the process. The array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progress in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling expression studies and/or systematic analyses of testicular proteomes in entire organs or isolated cells from various species. We consider the pros and cons of proteomics for studying the testicular germ cell gene expression program. Finally, we address the use of protein datasets, through integrative genomics (i.e., combining genomics, transcriptomics, and proteomics), bioinformatics, and modelling.
Systems Biology in Reproductive Medicine

hal-00877749
https://hal.archives-ouvertes.fr/hal-00877749
DOI : 10.3109/19396368.2012.691943
PUBMED : 22788530

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : Nucleotide diversity was assessed within nine candidate genes (in total 4.6 kb) for the time of bud burst in nine sessile oak (Quercus petraea) populations distributed in central and northern Europe. The sampled populations were selected on the basis of their contrasting time of bud burst observed in common garden experiments (provenance tests). The candidate genes were selected according to their expression profiles during the transition from quiescent to developing buds and/or their functional role in model plants. The overall nucleotide diversity was large (pi(tot) - 6.15 x 10(-3); pi(silent) - 11.2 x 10(-3)), but population differentiation was not larger than for microsatellites. No outlier single-nucleotide polymorphism (SNP), departing from neutral expectation, was found among the total of 125 SNPs. These results contrasted markedly with the significant associations that were observed between the candidate genes and bud burst in segregating populations. Quantitative trait loci (QTLs) for bud burst were identified for 13 year*site seasonal observations in a cloned mapping pedigree. Nineteen QTLs were detected, and QTLs located on linkage groups 2, 5 and 9 contributed repeatedly to more than 12% of the phenotypic variation of the trait. Eight genes were polymorphic in the two parents of the pedigree and could be mapped on the existing genetic map. Five of them located within the confidence intervals of QTLs for bud burst. Interestingly, four of them located within the three QTLs exhibiting the largest contributions to bud burst.
ISSN: 0018-067X

hal-01032156
https://hal.archives-ouvertes.fr/hal-01032156
DOI : 10.1038/hdy.2009.170

Éditeur(s) : HAL CCSD
Résumé : Visceral leishmaniasis is a life-threatening systemic disease caused by Leishmania protozoans, L. donovani and L. infantum, which invade mononuclear phagocytes in the lymphoid organs and the liver. The control of the hepatic parasite burden depends on the granuloma formation, which is favored by a Th1 immune response in a Th2 tissue microenvironment. The aim of this work was to study the role of the recently described Th2 cytokine IL-33 in this complex immune response, which remains partially misunderstood. IL-33 dosages in different patient sera and IL-33+ cells detected in the liver of a patient from Rennes suggested that IL-33 could be a biomarker for active visceral leishmaniasis. As IL-33 was described in hepatic stellate cells during chronic hepatitis, these cells were exposed to L. donovani in primary culture. The cell permissivity to L. donovani and the parasite persistence during a long term culture led us to propose hepatic stellate cells as a new type of sanctuary cells, which could partially explain asymptomatic carriage. However, these cells were apparently not the main source of IL-33 during visceral leishmaniasis. In infected BALB/c and C57BL/6 mice, IL-33 was detected in the liver in non stellate cells preferentially localized in granulomas. The presence of cells expressing its specific receptor ST2 in the liver led us to explore the role of the IL-33/ST2 axis. BALB/c mice deficient in ST2 or treated with recombinant IL-33 and infected with L. donovani revealed that IL-33 downregulates the expression of Th1 key cytokines (IL-12, IFN-γ) and the recruitment of neutrophils and monocytes. Finally, IL-33 acts as a susceptibility factor during visceral leishmaniasis. Besides, the model of L. donovani infected C57BL/6 mice deficient in IL-33 or treated with recombinant IL-33 suggests possible differential roles of IL-33 depending on the immune environment related to the host genetic background.
La leishmaniose viscérale est une maladie systémique mortelle en l’absence de traitement. Elle est due aux protozoaires Leishmania donovani et L. infantum, parasites des phagocytes mononucléés, capables d’envahir les organes lymphoïdes et le foie. Le contrôle de l’infection hépatique repose sur la mise en place d’une réponse granulomateuse efficace, promue par une réponse immunitaire Th1, dans un environnement tissulaire Th2. L’objectif de ce travail était l'étude du rôle d’une cytokine Th2 récemment décrite, l’IL-33, dans cette réponse hépatique complexe encore partiellement incomprise. Des dosages d’IL-33 sur des sérums de patients et la détection de cellules IL-33+ dans le foie d’un patient rennais ont placé l’IL-33 comme un biomarqueur possible de la maladie active. L’IL-33 étant exprimée dans les cellules étoilées du foie au cours d’hépatites chroniques, ces cellules ont été exposées à L. donovani. Leur permissivité aux leishmanies sans toxicité apparente ni perturbation de leurs propriétés fonctionnelles, ainsi que la persistance des leishmanies sur une culture de plusieurs semaines, nous ont conduit à proposer les cellules étoilées comme cellules sanctuaires possibles pour les leishmanies viscérotropes, contribuant donc potentiellement au portage asymptomatique. En revanche, elles ne sont pas apparues comme une source majeure d'IL-33 au cours de la leishmaniose viscérale. Chez des souris C57BL/6 et BALB/c infectées par L. donovani, l'IL-33 a été observée dans des cellules ne s'apparentant pas à des cellules étoilées, et principalement localisées dans les granulomes. Des cellules exprimant son récepteur ST2 ayant été également observées dans le foie, un rôle de l’axe IL-33/ST2 a été recherché. Les résultats obtenus chez des souris BALB/c déficientes en ST2 ou traitées par de l'IL-33 recombinante suggèrent que l'IL-33 régule négativement l'expression de cytokines Th1 (IL-12, IFN-γ) et l'infiltrat de neutrophiles et monocytes dans le foie, limitant ainsi le contrôle de la charge parasitaire. Ainsi, l'IL-33 semble être un facteur de susceptibilité pour la leishmaniose viscérale. En parallèle, des travaux entrepris sur des souris C57BL/6 infectées par L. donovani suggèrent de possibles rôles différentiels de l'IL-33 en fonction de l'environnement immunitaire inhérent au fond génétique de l'hôte.
https://tel.archives-ouvertes.fr/tel-01126847

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B002
tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847/document
https://tel.archives-ouvertes.fr/tel-01126847/file/2013REN1B002.pdf