Viability of brown trout embryos positively linked to melanin-based but negatively to carotenoid-based colours of their fathers.

'Good-genes' models of sexual selection predict significant additive genetic variation for fitness-correlated traits within populations to be revealed by phenotypic traits. To test this prediction, we sampled brown trout (Salmo trutta) from their natural spawning place, analysed their carotenoid-based red and melanin-based dark skin colours and tested whether these colours can be used to predict offspring viability. We produced half-sib families by in vitro fertilization, reared the resulting embryos under standardized conditions, released the hatchlings into a streamlet and identified the surviving juveniles 20 months later with microsatellite markers. Embryo viability was revealed by the sires' dark pigmentation: darker males sired more viable offspring. However, the sires' red coloration correlated negatively with embryo survival. Our study demonstrates that genetic variation for fitness-correlated traits is revealed by male colour traits in our study population, but contrary to predictions from other studies, intense red colours do not signal good genes.

Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults.

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain.

Unravelling the interaction between tectonic and sedimentary processes during lithospheric thinning in the Alpine Tethys margins

The discovery of exhumed continental mantle and hyper-extended crust in present-day magma-poor rifted margins is at the origin of a paradigm shift within the research field of deep-water rifted margins. It opened new questions about the strain history of rifted margins and the nature and composition of sedimentary, crustal and mantle rocks in rifted margins. Thanks to the benefit of more than one century of work in the Alps and access to world-class outcrops preserving the primary relationships between sediments and crustal and mantle rocks from the fossil Alpine Tethys margins, it is possible to link the subsidence history and syn-rift sedimentary evolution with the strain distribution observed in the crust and mantle rocks exposed in the distal rifted margins. In this paper, we will focus on the transition from early to late rifting that is associated with considerable crustal thinning and a reorganization of the rift system. Crustal thinning is at the origin of a major change in the style of deformation from high-angle to low-angle normal faulting which controls basin-architecture, sedimentary sources and processes and the nature of basement rocks exhumed along the detachment faults in the distal margin. Stratigraphic and isotopic ages indicate that this major change occurred in late Sinemurian time, involving a shift of the syn-rift sedimentation toward the distal domain associated with a major reorganization of the crustal structure with exhumation of lower and middle crust. These changes may be triggered by mantle processes, as indicated by the infiltration of MOR-type magmas in the lithospheric mantle, and the uplift of the Brianconnais domain. Thinning and exhumation of the crust and lithosphere also resulted in the creation of new paleogeographic domains, the Proto Valais and Liguria-Piemonte domains. These basins show a complex, 3D temporal and spatial evolution that might have evolved, at least in the case of the Liguria-Piemonte basin, in the formation of an embryonic oceanic crust. The re-interpretation of the rift evolution and the architecture of the distal rifted margins in the Alps have important implications for the understanding of rifted margins worldwide, but also for the paleogeographic reconstruction of the Alpine domain and its subsequent Alpine compressional overprint.

Visual-gustatory interaction: orbitofrontal and insular cortices mediate the effect of high-calorie visual food cues on taste pleasantness.

Vision provides a primary sensory input for food perception. It raises expectations on taste and nutritional value and drives acceptance or rejection. So far, the impact of visual food cues varying in energy content on subsequent taste integration remains unexplored. Using electrical neuroimaging, we assessed whether high- and low-calorie food cues differentially influence the brain processing and perception of a subsequent neutral electric taste. When viewing high-calorie food images, participants reported the subsequent taste to be more pleasant than when low-calorie food images preceded the identical taste. Moreover, the taste-evoked neural activity was stronger in the bilateral insula and the adjacent frontal operculum (FOP) within 100 ms after taste onset when preceded by high- versus low-calorie cues. A similar pattern evolved in the anterior cingulate (ACC) and medial orbitofrontal cortex (OFC) around 180 ms, as well as, in the right insula, around 360 ms. The activation differences in the OFC correlated positively with changes in taste pleasantness, a finding that is an accord with the role of the OFC in the hedonic evaluation of taste. Later activation differences in the right insula likely indicate revaluation of interoceptive taste awareness. Our findings reveal previously unknown mechanisms of cross-modal, visual-gustatory, sensory interactions underlying food evaluation.

Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX.

BACKGROUND: NR2E3 (PNR) is an orphan nuclear receptor essential for proper photoreceptor determination and differentiation. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S-) cone syndrome (ESCS) and, more recently, with autosomal dominant retinitis pigmentosa (adRP). NR2E3 acts as a suppressor of the cone generation program in late mitotic retinal progenitor cells. In adult rod photoreceptors, NR2E3 represses cone-specific gene expression and acts in concert with the transcription factors CRX and NRL to activate rod-specific genes. NR2E3 and CRX have been shown to physically interact in vitro through their respective DNA-binding domains (DBD). The DBD also contributes to homo- and heterodimerization of nuclear receptors. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed NR2E3 homodimerization and NR2E3/CRX complex formation in an in vivo situation by Bioluminescence Resonance Energy Transfer (BRET(2)). NR2E3 wild-type protein formed homodimers in transiently transfected HEK293T cells. NR2E3 homodimerization was impaired in presence of disease-causing mutations in the DBD, except for the p.R76Q and p.R104W mutant proteins. Strikingly, the adRP-linked p.G56R mutant protein interacted with CRX with a similar efficiency to that of NR2E3 wild-type and p.R311Q proteins. In contrast, all other NR2E3 DBD-mutant proteins did not interact with CRX. The p.G56R mutant protein was also more effective in abolishing the potentiation of rhodospin gene transactivation by the NR2E3 wild-type protein. In addition, the p.G56R mutant enhanced the transrepression of the M- and S-opsin promoter, while all other NR2E3 DBD-mutants did not. CONCLUSIONS/SIGNIFICANCE: These results suggest different disease mechanisms in adRP- and ESCS-patients carrying NR2E3 mutations. Titration of CRX by the p.G56R mutant protein acting as a repressor in trans may account for the severe clinical phenotype in adRP patients.

Regions of mouse mammary tumor virus superantigen involved in interaction with the major histocompatibility complex class II I-A molecule.

To study the major histocompatibility complex class II I-E dependence of mouse mammary tumor virus (MMTV) superantigens, we constructed hybrids between the I-E-dependent MMTV(GR) and the I-E-independent mtv-7 superantigens and tested them in vivo. Our results suggest that, although the C-terminal third mediates I-A interaction, additional binding sites are located elsewhere in the superantigen.

Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion.

Objective-Inflammation and proteolysis crucially contribute to myocardial ischemia and reperfusion injury. The extracellular matrix metalloproteinase inducer EMMPRIN (CD147) and its ligand cyclophilin A (CyPA) may be involved in both processes. The aim of the study was to characterize the role of the CD147 and CyPA interplay in myocardial ischemia/reperfusion (I/R) injury.Methods and Results-Immunohistochemistry showed enhanced expression of CD147 and CyPA in myocardial sections from human autopsies of patients who had died from acute myocardial infarction and from mice at 24 hours after I/R. At 24 hours and 7 days after I/R, the infarct size was reduced in CD147(+/-) mice vs CD147(+/+) mice (C57Bl/6), in mice (C57Bl/6) treated with monoclonal antibody anti-CD147 vs control monoclonal antibody, and in CyPA(-/-) mice vs CyPA(+/+) mice (129S6/SvEv), all of which are associated with reduced monocyte and neutrophil recruitment at 24 hours and with a preserved systolic function at 7 days. The combination of CyPA(-/-) mice with anti-CD147 treatment did not yield further protection compared with either inhibition strategy alone. In vitro, treatment with CyPA induced monocyte chemotaxis in a CD147-and phosphatidylinositol 3-kinase-dependent manner and induced monocyte rolling and adhesion to endothelium (human umbilical vein endothelial cells) under flow in a CD147-dependent manner.Conclusion-CD147 and its ligand CyPA are inflammatory mediators after myocardial ischemia and reperfusion and represent potential targets to prevent myocardial I/R injury.

Receptor binding and cell entry of Old World arenaviruses reveal novel aspects of virus-host interaction.

Ten years ago, the first cellular receptor for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the highly pathogenic Lassa virus (LASV) was identified as alpha-dystroglycan (alpha-DG), a versatile receptor for proteins of the extracellular matrix (ECM). Biochemical analysis of the interaction of alpha-DG with arenaviruses and ECM proteins revealed a strikingly similar mechanism of receptor recognition that critically depends on specific sugar modification on alpha-DG involving a novel class of putative glycosyltransferase, the LARGE proteins. Interestingly, recent genome-wide detection and characterization of positive selection in human populations revealed evidence for positive selection of a locus within the LARGE gene in populations from Western Africa, where LASV is endemic. While most enveloped viruses that enter the host cell in a pH-dependent manner use clathrin-mediated endocytosis, recent studies revealed that the Old World arenaviruses LCMV and LASV enter the host cell predominantly via a novel and unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the virus is rapidly delivered to endosomes via an unusual route of vesicular trafficking that is largely independent of the small GTPases Rab5 and Rab7. Since infection of cells with LCMV and LASV depends on DG, this unusual endocytotic pathway could be related to normal cellular trafficking of the DG complex. Alternatively, engagement of arenavirus particles may target DG for an endocytotic pathway not normally used in uninfected cells thereby inducing an entry route specifically tailored to the pathogen's needs.

Proximate basis of the covariation between a melanin-based female ornament and offspring quality.

In contradiction to sexual selection theory, several studies showed that although the expression of melanin-based ornaments is usually under strong genetic control and weakly sensitive to the environment and body condition, they can signal individual quality. Covariation between a melanin-based ornament and phenotypic quality may result from pleiotropic effects of genes involved in the production of melanin pigments. Two categories of genes responsible for variation in melanin production may be relevant, namely those that trigger melanin production (yes or no response) and those that determine the amount of pigments produced. To investigate which of these two hypotheses is the most likely, I reanalysed data collected from barn owls ( Tyto alba). The underparts of this bird vary from immaculate to heavily marked with black spots of varying size. Published cross-fostering experiments have shown that the proportion of the plumage surface covered with black spots, a eumelanin composite trait so-called "plumage spottiness", in females positively covaries with offspring humoral immunocompetence, and negatively with offspring parasite resistance (i.show $132#e. the ability to reduce fecundity of ectoparasites) and fluctuating asymmetry of wing feathers. However, it is unclear which component of plumage spottiness causes these relationships, namely genes responsible for variation in number of spots or in spot diameter. Number of spots reflects variation in the expression of genes triggering the switch from no eumelanin production to production, whereas spot diameter reflects variation in the expression of genes determining the amount of eumelanin produced per spot. In the present study, multiple regression analyses, performed on the same data sets, showed that humoral immunocompetence, parasite resistance and wing fluctuating asymmetry of cross-fostered offspring covary with spot diameter measured in their genetic mother, but not with number of spots. This suggests that genes responsible for variation in the quantity of eumelanin produced per spot are responsible for covariation between a melanin ornament and individual attributes. In contrast, genes responsible for variation in number of black spots may not play a significant role. Covariation between a eumelanin female trait and offspring quality may therefore be due to an indirect effect of melanin production.

An interaction network of the mammalian COP9 signalosome identifies Dda1 as a core subunit of multiple Cul4-based E3 ligases.

The COP9 signalosome (CSN) is an evolutionarily conserved macromolecular complex that interacts with cullin-RING E3 ligases (CRLs) and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. The CSN sequesters inactive CRL4(Ddb2), which rapidly dissociates from the CSN upon DNA damage. Here we systematically define the protein interaction network of the mammalian CSN through mass spectrometric interrogation of the CSN subunits Csn1, Csn3, Csn4, Csn5, Csn6 and Csn7a. Notably, we identified a subset of CRL complexes that stably interact with the CSN and thus might similarly be activated by dissociation from the CSN in response to specific cues. In addition, we detected several new proteins in the CRL-CSN interactome, including Dda1, which we characterized as a chromatin-associated core subunit of multiple CRL4 proteins. Cells depleted of Dda1 spontaneously accumulated double-stranded DNA breaks in a similar way to Cul4A-, Cul4B- or Wdr23-depleted cells, indicating that Dda1 interacts physically and functionally with CRL4 complexes. This analysis identifies new components of the CRL family of E3 ligases and elaborates new connections between the CRL and CSN complexes.

The adaptive function of melanin-based coloration in the tawny owl (Strix aluco) ; the proximate role of the melanocortin system

Colour polymorphism is common in wild population. One of the main questioning of evolutionary biologists is to understand how different colour variants could have evolved and be maintained in fluctuating environments, a selective process that forces individuals to constantly adapt their strategies in order to survive. This issue is particularly true for traits that are genetically inherited. Natural selection erodes genotypes with lowest fitness (less adapted), reducing in turn global genetic variation within population. In this context, the study of the evolution and maintenance of melanin- based coloration is relevant since inter-individual variation in the deposition of these pigments is common in animal and plant kingdoms and is under strong genetic control. In this thesis, I focus on the specific case of the tawny owl (Strix aluco), a species displaying continuous variation in reddish pheomelanin-based coloration. Interestingly, empirical studies highlighted covariations between melanin-based coloration and important behavioural, physiological and life history traits. Recently, a genetic model pointed out the melanocortin system and their pleiotropic effects as a potential regulator of these covariations. Accordingly, this PhD thesis further investigates colour-specific behavioural, physiological, or life history strategies, while examining the proximate mechanisms underlying these reaction norms. We found that differently coloured tawny owls differently resolve fundamental trade-off between offspring number and quality (Chapter 1), light melanic individuals producing many low- quality offspring and dark, melanic ones producing few high-quality offspring. These reproductive strategies are likely to induce alternative physiological constraints. Indeed, we demonstrated that light melanic individuals produced higher levels of reactive oxygen species (ROS, Chapter 2), but also expressed higher levels of antioxidant (GSH, Chapters 2 & 3). Interestingly, we showed that light melanic breeding females could modulate their POMC prohormone levels according to the environmental conditions, while dark reddish ones produced constant levels of this prohormone {Chapter 4). Finally, we highlighted colour-specific patterns of prohormone convertase 1 (PCI) gene expression (Chapter 5), an enzyme responsible for POMC prohormone processing to ACTH and a- MSH, for instance. Altogether, these results provide strong evidence of colour-specific strategies, light and melanic tawny owls better coping with stressful and relaxed environments, respectively. Variation in melanin-based coloration is likely to be maintained by the heterogeneity of our study area and strong environmental stochasticity within and between years, these process favouring differently coloured tawny owls at different periods of time. From a proximate point of view, this PhD thesis supports the hypothesis that covariations between phenotypic traits and melanin-based coloration stems from the melanocortin system, especially the fundamental role of POMC gene expression and its processing to melanocortin peptides. - Le polymorphisme de couleur est une variation phénotypique très fréquente dans la nature. En biologie évolutive, une des problématiques clés est donc de comprendre comment différent morphes de couleur peuvent être apparus et maintenus au cours du temps dans des environnements aussi variables que les nôtres, surtout que ces fluctuations forcent ces morphes à s'adapter constamment pour assurer leur survie. Cette thématique est particulièrement réelle lorsque les variations phénotypiques sont héréditaires et donc sous forte influence génétique. La sélection naturelle a en effet le pouvoir d'éroder rapidement la variation génétique en éliminant les génotypes mal adaptés. Dans ce sens, l'étude de l'évolution, et de la maintenance de la coloration mélanique est donc tout à fait pertinente car la variation de coloration entre individus est très répandue à travers les règnes animal et végétal et sous forte influence génétique. Dans cette thèse, je me suis concentré sur le cas spécifique de la chouette hulotte (Strix aluco), une espèce présentant une variation continue dans la déposition de pigments pheomélaniques roux. De précédentes études ont déjà montré que cette variation de coloration était associée avec des variations de traits comportementaux, physiologiques ou d'histoire de vie. Récemment, une étude a souligné l'importance du système des mélanocortines et de leurs effets pléiotropes dans la régulation de ces covariations. En conséquence, cette thèse de doctoral a pour but d'étudier un peu plus les stratégies comportementales, physiologiques ou d'histoire de vie spécifiques à chaque morphe de couleur, tout en examinant un peu plus les mécanismes proximaux potentiellement à la base de ces normes de réactions. Nous constatons tout d'abord que les morphes de couleurs étaient associés à différentes stratégies dans la résolution de compromis telle que la production de beaucoup de jeunes ou des jeunes de qualité (Chapitre 1). Les morphes gris (dit peu mélaniques) ont tendance à produire beaucoup de jeunes mains de moindre qualité, alors que les morphes roux (dit fortement mélaniques) produisent moins de jeunes mais de meilleure qualité. Ces stratégies sont susceptibles alors d'induire certaines contraintes physiologiques. Par exemple, nous montrons que les morphes gris produisent plus de dérivés réactifs de l'oxygène (ROS, Chapitre 2), mais aussi plus d'antioxydants (GSH, Chapitres 2 & 3). Nous montrons ensuite que les femelles grises ont une plus grande capacité à moduler leur niveau de POMC prohormone dans le sang en fonction des conditions environnementales, alors que les femelles rousses gardent un niveau constant (Chapitre 4). Finalement, nous démontrons que les patterns d'expression du gène codant pour la prohormone convertase 1 varient chez des jeunes issus de parents gris ou roux (Chapitre 5). Ceci est particulièrement intéressant car cette enzyme permet de scinder la POMC prohormone en plusieurs peptides importants tels que l'ACTH ou l'a-MSH. En conclusion, ces résultats démontrent qu'il y a bel et bien des stratégies évolutives différentes entre les morphes de couleurs, les chouettes hulottes grises et rousses étant respectivement plus adaptés à des environnements stressants ou favorables. L'hétérogénéité de notre zone d'étude et la stochasticité environnementale qui caractérise ses habitats pourraient donc agir comme une source de sélection temporelle, laquelle favoriserait les différents morphes de couleurs à diverses périodes. D'un point de vue plus proximale maintenant, cette thèse de doctorat soutient l'hypothèse que les covariations observées entre la coloration mélanique et des traits phénotypiques importants sont modulées par les effets pléiotropes du système des mélanocortines, et met en avant le rôle prépondérant que pourrait jouer l'expression du gène POMC et sa post traduction en mélanocortines.

Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone.

The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue-inducer cells with stromal lymphoid tissue-organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue-inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin alpha(1)beta(2) signaling. Thus, crosstalk between lymphoid tissue-inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.

7Ni-O chemical interaction and the transition temperature of Ni-doped Bi2Sr2Ca1Cu2O8

We find that even very low Ni doping levels of high-quality Bi2Sr2Ca1Cu2O8 single crystals strongly affect the transition temperature T(c). We also observed that T(c) is not related to the total Ni concentration, but only to that of Ni engaged in NiO-type bonds. By controlling the temperature during crystal growth, one can modify the relative weight of Ni in NiO-type bonds with respect to other configurations-and therefore T(c).