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Threat perception and familiarity moderate the androgen response to competition in women
Get PDFSocial interactions elicit androgen responses whose function has been posited to be the adjustment of androgen-dependent behaviors to social context. The activation of this androgen response is known to be mediated and moderated by psychological factors. In this study we tested the hypothesis that the testosterone (T) changes after a competition are not simply related to its outcome, but rather to the way the subject evaluates the event. In particular we tested two evaluative dimensions of a social interaction: familiarity with the opponent and the subjective evaluation of the outcome as threat or challenge. Challenge/threat occurs in goal relevant situations and represent different motivational states arising from the individuals' subjective evaluation of the interplay between the task demands and coping resources possessed. For challenge the coping resources exceed the task demands, while threat represents a state where coping resources are insufficient to meet the task demands. In this experiment women competed in pairs, against a same sex opponent using the number tracking test as a competitive task. Losers appraised the competition outcome as more threatening than winners, and displayed higher post-competition T levels than winners. No differences were found either for cortisol (C) or for dehydroepiandrosterone. Threat, familiarity with the opponent and T response were associated only in the loser condition. Moderation analysis suggests that for the women that lost the competition the effect of threat on T is moderated by familiarity with the opponent.FCT grant: (RG-LVT-331-2352), FCT PhD fellowship (SFRH/BD/68528/2010)
Comparative analysis of Streptococcus pneumoniae transmission in Portuguese and Finnish day-care centres
Get PDFDay-care centre (DCC) attendees play a central role in maintaining the circulation of Streptococcus pneumoniae (pneumococcus) in the population. The prevalence of pneumococcal carriage is highest in DCC attendees but varies across countries and is found to be consistently lower in Finland than in Portugal. We compared key parameters underlying pneumococcal transmission in DCCs to understand which of these contributed to the observed differences in carriage prevalence.PneumoCarr Consortium, Bill and Melinda Gates Foundation grant
A DNA Metabarcoding Study of a Primate Dietary Diversity and Plasticity across Its Entire Fragmented Range
Get PDFIn tropical regions, most primary ecosystems have been replaced by mosaic landscapes in which species must cope with a large shift in the distribution of their habitat and associated food resources. Primates are particularly vulnerable to habitat modifications. Most species persist in small fragments surrounded by complex human-mediated matrices whose structure and connectivity may strongly influence their dispersal and feeding behavior. Behavioral plasticity appears to be a crucial parameter governing the ability of organisms to exploit the resources offered by new matrix habitats and thus to persist in fragmented habitats. In this study, we were interested in the dietary plasticity of the golden-crowned sifaka (Propithecus tattersalli), an endangered species of lemur, found only in the Daraina region in north-eastern Madagascar. We used a DNA-based approach combining the barcoding concept and Illumina next-generation sequencing to (i) describe the species diet across its entire range and (ii) evaluate the influence of landscape heterogeneity on diet diversity and composition. Faeces from 96 individuals were sampled across the entire species range and their contents were analyzed using the trnL metabarcoding approach. In parallel, we built a large DNA reference database based on a checklist of the plant species of the Daraina region. Our results suggest that golden-crowned sifakas exhibit remarkable dietary diversity with at least 130 plant species belonging to 80 genera and 49 different families. We highlighted an influence of both habitat type and openness on diet composition suggesting a high flexibility of foraging strategies. Moreover, we observed the presence of numerous cultivated and naturalized plants in the faeces of groups living in forest edge areas. Overall, our findings support our initial expectation that P. tattersalli is able to cope with the current level of alteration of the landscape and confirm our previous results on the distribution and the dispersal ability of this species.Institut Francais de la Biodiversité, Programme Biodiversité de l'Océan Indien (reference no.CD-AOO1-07-003), Laboratoire d’Excellence (LABEX) entitled TULIP (ANR-10-LABX-41), Conservatoire et Jardin botaniques de la Ville de Genève, Conservation International (CBC fund), Fondation Jean-Marcel Aubert, Vontobel Stiftung
A Major Facilitator Superfamily Transporter Plays a Dual Role in Polar Auxin Transport and Drought Stress Tolerance in Arabidopsis
Get PDFMany key aspects of plant development are regulated by the polarized transport of the phytohormone auxin. Cellular auxin efflux, the rate-limiting step in this process, has been shown to rely on the coordinated action of PIN-formed (PIN) and B-type ATP binding cassette (ABCB) carriers. Here, we report that polar auxin transport in the Arabidopsis thaliana root also requires the action of a Major Facilitator Superfamily (MFS) transporter, Zinc-Induced Facilitator-Like 1 (ZIFL1). Sequencing, promoter-reporter, and fluorescent protein fusion experiments indicate that the full-length ZIFL1.1 protein and a truncated splice isoform, ZIFL1.3, localize to the tonoplast of root cells and the plasma membrane of leaf stomatal guard cells, respectively. Using reverse genetics, we show that the ZIFL1.1 transporter regulates various root auxin-related processes, while the ZIFL1.3 isoform mediates drought tolerance by regulating stomatal closure. Auxin transport and immunolocalization assays demonstrate that ZIFL1.1 indirectly modulates cellular auxin efflux during shootward auxin transport at the root tip, likely by regulating plasma membrane PIN2 abundance. Finally, heterologous expression in yeast revealed that ZIFL1.1 and ZIFL1.3 share H(+)-coupled K(+) transport activity. Thus, by determining the subcellular and tissue distribution of two isoforms, alternative splicing dictates a dual function for the ZIFL1 transporter. We propose that this MFS carrier regulates stomatal movements and polar auxin transport by modulating potassium and proton fluxes in Arabidopsis cells.FCT fellowships: (SFRH/BPD/44640/2008, SFRH/BPD/81221/2011)
ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs inArabidopsisroot tip
Get PDFCell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN 2 carrier in epidermal root tip cells under conditions normally triggering PIN 2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN 1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots.FCT fellowship: (SFRH/BPD/44640/2008)
ABI1 and PP2CA Phosphatases Are Negative Regulators of Snf1-Related Protein Kinase1 Signaling in Arabidopsis
No full textPlant survival under environmental stress requires the integration of multiple signaling pathways into a coordinated response, but the molecular mechanisms underlying this integration are poorly understood. Stress-derived energy deprivation activates the Snf1-related protein kinases1 (SnRK1s), triggering a vast transcriptional and metabolic reprogramming that restores homeostasis and promotes tolerance to adverse conditions. Here, we show that two clade A type 2C protein phosphatases (PP2Cs), established repressors of the abscisic acid (ABA) hormonal pathway, interact with the SnRK1 catalytic subunit causing its dephosphorylation and inactivation. Accordingly, SnRK1 repression is abrogated in double and quadruple pp2c knockout mutants, provoking, similarly to SnRK1 overexpression, sugar hypersensitivity during early seedling development. Reporter gene assays and SnRK1 target gene expression analyses further demonstrate that PP2C inhibition by ABA results in SnRK1 activation, promoting SnRK1 signaling during stress and once the energy deficit subsides. Consistent with this, SnRK1 and ABA induce largely overlapping transcriptional responses. Hence, the PP2C hub allows the coordinated activation of ABA and energy signaling, strengthening the stress response through the cooperation of two key and complementary pathways.Marie Curie IRG grants; the EMBO Installation program; Marie Curie Actions grant: (FP7-People-2010-ITN); FCT grants: (PTDC/AGR-AAM/104939/2008, SFRH/BPD/47280/2008, SFRH/BD/33563/2008, SFRH/BD/51627/2011, SFRH/BPD/79255/2011); Portugal-Spain Bilateral Collaboration program Ações integradas: (Ação E-26/10); Generalitat de Catalunya PhD grant: (FI-AR067443); Ministerio de Ciencia e Innovación grants: (BIO2011-23446, PT2009-0155); Junta para Ampliación de Estudios e Investigaciones Científicas-Consejo Superior de Investigaciones Cientificas fellowship; Juan de la Cierva contract
Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells
Get PDFTelomeres protect eukaryotic chromosomes from illegitimate end-to-end fusions. When this function fails, dicentric chromosomes are formed, triggering breakage-fusion-bridge cycles and genome instability. How efficient is this protection mechanism in normal cells is not fully understood. We created a positive selection assay aimed at capturing chromosome-end fusions in Schizosaccharomyces pombe. We placed telomere sequences with a head to head arrangement in an intron of a selectable marker contained on a plasmid. By linearizing the plasmid between the telomere sequences, we generated a stable mini-chromosome that fails to express the reporter gene. Whenever the ends of the mini-chromosome join, the marker gene is reconstituted and fusions are captured by direct selection. Using telomerase mutants, we recovered several fusion events that lacked telomere sequences. The end-joining reaction involved specific homologous subtelomeric sequences capable of forming hairpins, suggestive of ssDNA stabilization prior to fusing. These events occurred via microhomology-mediated end-joining (MMEJ)/single-strand annealing (SSA) repair and also required MRN/Ctp1. Strikingly, we were able to capture spontaneous telomere-to-telomere fusions in unperturbed cells. Similar to disruption of the telomere regulator Taz1/TRF2, end-joining reactions occurred via non-homologous end-joining (NHEJ) repair. Thus, telomeres undergo fusions prior to becoming critically short, possibly through transient deprotection. These dysfunction events induce chromosome instability and may underlie early tumourigenesis.FCT fellowship: (SFRH/BD/62050/2009), Association for International Cancer Research (Ref:06-396)
Dynamical modeling and analysis of large cellular regulatory networks
Get PDFThe dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.EU FP7 (APOSYS large scale project), EU EraSysBio+ program (project ModHeart), ANR (Project Grant ANR-08-SYSC-003), Belgian Science Policy Office (IAP BioMaGNet)
Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomes
Get PDFCentromeres are the site of kinetochore formation during mitosis. Centromere protein A (CENP-A), the centromere-specific histone H3 variant, is essential for the epigenetic maintenance of centromere position. Previously we showed that newly synthesized CENP-A is targeted to centromeres exclusively during early G1 phase and is subsequently maintained across mitotic divisions. Using SNAP-based fluorescent pulse labeling, we now demonstrate that cell cycle-restricted chromatin assembly at centromeres is unique to CENP-A nucleosomes and does not involve assembly of other H3 variants. Strikingly, stable retention is restricted to the CENP-A/H4 core of the nucleosome, which we find to outlast general chromatin across several cell divisions. We further show that cell cycle timing of CENP-A assembly is independent of centromeric DNA sequences and instead is mediated by the CENP-A targeting domain. Unexpectedly, this domain also induces stable transmission of centromeric nucleosomes, independent of the CENP-A deposition factor HJURP. This demonstrates that intrinsic properties of the CENP-A protein direct its cell cycle-restricted assembly and induces quantitative mitotic transmission of the CENP-A/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position.FCT fellpwships: (SFRH/BD/74284/2010, SFRH/BPD/69115/2010), National Institutes of Health grant: (GM082989), Burroughs Wellcome Fund (Career Award in the Biomedical Sciences), Rita Allen Foundation
Scholar Award, Instituto Gulbenkian de Ciência, European Commission FP7 Program, EMBO
Path2Models: large-scale generation of computational models from biochemical pathway maps
Get PDFSystems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.US National Institute of General Medical Sciences grant: (GM070923), Federal Ministry of Education and
Research (BMBF, German) grants: (0315756, 01GS08134), Marie Curie International Outgoing Fellowship, US National Institute of General Medical Sciences grant: (GM080219), BBSRC grant: (BB/J019259/1), EMBL-EBI, nnovative Medicines Initiative Joint Undertaking under grant agreement: (115156