Instituto Gulbenkian de Ciência

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    657 research outputs found

    Evidence for a Myotomal Hox/Myf Cascade Governing Nonautonomous Control of Rib Specification within Global Vertebral Domains

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    Hox genes are essential for the patterning of the axial skeleton. Hox group 10 has been shown to specify the lumbar domain by setting a rib-inhibiting program in the presomitic mesoderm (PSM). We have now produced mice with ribs in every vertebra by ectopically expressing Hox group 6 in the PSM, indicating that Hox genes are also able to specify the thoracic domain. We show that the information provided by Hox genes to specify rib-containing and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression. This information is then transmitted to the sclerotome by a system that includes FGF and PDGF signaling to produce vertebrae with or without ribs at different axial levels. Our findings offer a new perspective of how Hox genes produce global patterns in the axial skeleton and support a redundant nonmyogenic role of Myf5 and Myf6 in rib formation.Fundação para a Ciência e a Tecnologia grants: (PTDC/BIA-BCM/71619/2006, POCTI-ISFL-4-664, SFRH/BD/27306/2006, SFRH/BPD/26668/2006)

    Landscape genetics of an endangered lemur (Propithecus tattersalli) within its entire fragmented range

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    Habitat fragmentation may strongly reduce individuals' dispersal among resource patches and hence influence population distribution and persistence. We studied the impact of landscape heterogeneity on the dispersal of the golden-crowned sifaka (Propithecus tattersalli), an endangered social lemur species living in a restricted and highly fragmented landscape. We combined spatial analysis and population genetics methods to describe population units and identify the environmental factors which best predict the rates and patterns of genetic differentiation within and between populations. We used non-invasive methods to genotype 230 individuals at 13 microsatellites in all the main forest fragments of its entire distribution area. Our analyses suggest that the Manankolana River and geographical distance are the primary structuring factors, while a national road crossing the region does not seem to impede gene flow. Altogether, our results are in agreement with a limited influence of forest habitat connectivity on gene flow patterns (except for North of the species' range), suggesting that dispersal is still possible today among most forest patches for this species. Within forest patches, we find that dispersal is mainly among neighbouring social groups, hence confirming previous behavioural observation

    Spatial Variation in Density and Total Size Estimates in Fragmented Primate Populations: The Golden-Crowned Sifaka (Propithecus tattersalli)

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    The golden-crowned sifaka (Propithecus tattersalli) is an endangered lemur species found only in the Daraina region, a very restricted area in north-eastern Madagascar. Its forest habitat is highly fragmented and expected to suffer from significant changes in the near future. The species is poorly known and only one census study, carried out in 2000, has ever been published. It is thus crucial to update the conservation status of the golden-crowned sifaka. before major anthropogenic environmental changes take place. Using the line-transect approach, we estimated the species density in the main forest fragments located in both the peripheral and central parts of the distribution range, including both protected and unprotected areas. In parallel, we tried to determine whether an edge effect could be detected by comparing densities at different distances from the forest edges. We found important variation of sifaka densities among forest fragments. The total species abundance is thus difficult to determine, but we estimated that it is likely to be over 18,000, two to three times higher than previously thought. However, our data also suggested that most P. tattersalli live in forests located in the central part of the distribution range and that the estimated densities in the central part were high (> 80 individuals/km(2)). Two forest fragments, found to host a large part of the total population, are currently outside the managed area and their incorporation to the managed area is strongly recommended. Lastly, as expected for a folivorous and not heavily hunted species, our results are consistent with the hypothesis that this species does not experience a clear edge effect, at least during the first half of the dry season. This could be due to a high resiliency to habitat fragmentation or to the fact that fragmentation has been going on for some time

    Diversity and plasticity of Th cell types predicted from regulatory network modelling

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    Alternative cell differentiation pathways are believed to arise from the concerted action of signalling pathways and transcriptional regulatory networks. However, the prediction of mammalian cell differentiation from the knowledge of the presence of specific signals and transcriptional factors is still a daunting challenge. In this respect, the vertebrate hematopoietic system, with its many branching differentiation pathways and cell types, is a compelling case study. In this paper, we propose an integrated, comprehensive model of the regulatory network and signalling pathways controlling Th cell differentiation. As most available data are qualitative, we rely on a logical formalism to perform extensive dynamical analyses. To cope with the size and complexity of the resulting network, we use an original model reduction approach together with a stable state identification algorithm. To assess the effects of heterogeneous environments on Th cell differentiation, we have performed a systematic series of simulations considering various prototypic environments. Consequently, we have identified stable states corresponding to canonical Th1, Th2, Th17 and Treg subtypes, but these were found to coexist with other transient hybrid cell types that co-express combinations of Th1, Th2, Treg and Th17 markers in an environment-dependent fashion. In the process, our logical analysis highlights the nature of these cell types and their relationships with canonical Th subtypes. Finally, our logical model can be used to explore novel differentiation pathways in silico.French National Agency projects: (ANR-06-BYOS-0006, ANR-08-SYSC-003); Belgian Science Policy Office (IAP BioMaGNet); Calouste Gulbenkian Foundation

    Centrioles: active players or passengers during mitosis?

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    There is no public supplementary material available.Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as "the organ for cell division". However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio

    2BAD: an application to estimate the parental contributions during two independent admixture events

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    Several approaches have been developed to calculate the relative contributions of parental populations in single admixture event scenarios, including Bayesian methods. In many breeds and populations, it may be more realistic to consider multiple admixture events. However, no approach has been developed to date to estimate admixture in such cases. This report describes a program application, 2BAD (for 2-event Bayesian ADmixture), which allows the consideration of up to two independent admixture events involving two or three parental populations and a single admixed population, depending on the number of populations sampled. For each of these models, it is possible to estimate several parameters (admixture, effective sizes, etc.) using an approximate Bayesian computation approach. In addition, the program allows comparing pairs of admixture models, determining which is the most likely given data. The application was tested through simulations and was found to provide good estimates for the contribution of the populations at the two admixture events. We were also able to determine whether an admixture model was more likely than a simple split model

    Energy Signaling in the Regulation of Gene Expression during Stress

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    Maintenance of homeostasis is pivotal to all forms of life. In the case of plants, homeostasis is constantly threatened by the inability to escape environmental fluctuations, and therefore sensitive mechanisms must have evolved to allow rapid perception of environmental cues and concomitant modification of growth and developmental patterns for adaptation and survival. Re-establishment of homeostasis in response to environmental perturbations requires reprogramming of metabolism and gene expression to shunt energy sources from growth-related biosynthetic processes to defense, acclimation, and, ultimately, adaptation. Failure to mount an initial 'emergency' response may result in nutrient deprivation and irreversible senescence and cell death. Early signaling events largely determine the capacity of plants to orchestrate a successful adaptive response. Early events, on the other hand, are likely to be shared by different conditions through the generation of similar signals and before more specific responses are elaborated. Recent studies lend credence to this hypothesis, underpinning the importance of a shared energy signal in the transcriptional response to various types of stress. Energy deficiency is associated with most environmental perturbations due to their direct or indirect deleterious impact on photosynthesis and/or respiration. Several systems are known to have evolved for monitoring the available resources and triggering metabolic, growth, and developmental decisions accordingly. In doing so, energy-sensing systems regulate gene expression at multiple levels to allow flexibility in the diversity and the kinetics of the stress response.Marie Curie International Reintegration Grant: PIRG03-GA-2008-231020

    Cognitive and motivational requirements for the emergence of cooperation in a rat social game

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    Background: Game theory and the Prisoner's Dilemma (PD) game in particular, which captures the paradox of cooperative interactions that lead to benefits but entail costs to the interacting individuals, have constituted a powerful tool in the study of the mechanisms of reciprocity. However, in non-human animals most tests of reciprocity in PD games have resulted in sustained defection strategies. As a consequence, it has been suggested that under such stringent conditions as the PD game humans alone have evolved the necessary cognitive abilities to engage in reciprocity, namely, numerical discrimination, memory and control of temporal discounting. Methodology/Principal Findings: We use an iterated PD game to test rats (Rattus norvegicus) for the presence of such cognitive abilities by manipulating the strategy of the opponent, Tit-for-Tat and Pseudo-Random, or the relative size of the temptation to defect. We found that rats shape their behaviour according to the opponent's strategy and the relative outcome resulting from cooperative or defective moves. Finally, we show that the behaviour of rats is contingent upon their motivational state (hungry versus sated). Conclusions/Significance: Here we show that rats understand the payoff matrix of the PD game and the strategy of the opponent. Importantly, our findings reveal that rats possess the necessary cognitive capacities for reciprocity-based cooperation to emerge in the context of a prisoner's dilemma. Finally, the validation of the rat as a model to study reciprocity-based cooperation during the PD game opens new avenues of research in experimental neuroscience

    The utility of existing passerine microsatellite markers for genetic studies in endangered species: as demonstrated for a critically endangered forest bird endemic to Réunion Island, the Réunion cuckooshrike (Coracina newtoni)

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    Genetic data are increasingly recognized for their utility in conservation programs. However, many endangered species belong to families that have been understudied. Due to the urgency of their conservation status it is important to quickly identify polymorphic microsatellite loci from available resources. We show for the Re´union Cuckoo shrike Coracina newtoni, that this strategy can be very useful. Using 110 passerine microsatellite primer sets we identified eighteen polymorphic loci and tested them in 25 C. newtoni individuals. Following a Bonferroni correction one pair of loci displayed linkage disequilibriu

    Genomic Expression Program Involving the Haalp-Regulation in Saccharomyces cerevisiae response to acetic acid

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    The alterations occurring in yeast genomic expression during early response to acetic acid and the involvement of the transcription factor Haa1p in this transcriptional reprogramming are described in this study. Haa1p was found to regulate, directly or indirectly, the transcription of approximately 80% of the acetic acid-activated genes, suggesting that Haa1p is the main player in the control of yeast response to this weak acid. The genes identified in this work as being activated in response to acetic acid in a Haa1p-dependent manner include protein kinases, multidrug resistance transporters, proteins involved in lipid metabolism, in nucleic acid processing, and proteins of unknown function. Among these genes, the expression of SAP30 and HRK1 provided the strongest protective effect toward acetic acid. SAP30 encode a subunit of a histone deacetylase complex and HRK1 encode a protein kinase belonging to a family of protein kinases dedicated to the regulation of plasma membrane transporters activity. The deletion of the HRK1 gene was found to lead to the increase of the accumulation of labeled acetic acid into acid-stressed yeast cells, suggesting that the role of both HAA1 and HRK1 in providing protection against acetic acid is, at least partially, related with their involvement in the reduction of intracellular acetate concentration

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