56 research outputs found

    Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins

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    International audienceCRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages. Here we identify AcrIIA6, an Acr encoded in 33% of virulent Streptococcus thermophilus phage genomes. The X-ray structure of AcrIIA6 displays some features unique to this Acr family. We compare the activity of AcrIIA6 to those of other Acrs, including AcrIIA5 (also from S. thermophilus phages), and characterize their effectiveness against a range of CRISPR-Cas systems. Finally, we demonstrate that both Acr families from S. thermophilus phages inhibit Cas9-mediated genome editing of human cells

    Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1

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    Combination antiretroviral therapy (cART) can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704) which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2). 57704 also increased HIV-1 expression in 3 of 4 CD8+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110a isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency. © 2014 Doyon et al

    Un outil en os à usages multiples dans un contexte moustérien

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    La prolifération des cyanobactéries au Québec : une perspective de sciences sociales sur le risque et la gestion

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    Cette recherche qualitative à portée exploratoire porte sur les représentations sociales, les attitudes et les impacts associés au phénomène des cyanobactéries et s’inscrit dans une perspective constructiviste liée à l’écologie politique. Les cyanobactéries sont des microorganismes présents de façon naturelle dans la plupart des plans d’eau, et certaines espèces peuvent libérer des toxines susceptibles de causer des problèmes de santé chez les êtres humains, surtout si elles se trouvent en forte concentration. Au Québec, lorsque les risques sont jugés élevés, les autorités de santé publique émettent des mises en garde concernant la pratique d’activités nautiques et la consommation d’eau potable, mais la population ne s’y conforme pas toujours. Dans le but de mieux comprendre les attitudes des citoyens à l’égard des cyanobactéries et des mesures de santé publique, nous avons réalisé une enquête visant à identifier les significations attribuées à ce phénomène – en accordant une attention particulière aux représentations sociales du risque – ainsi que les autres facteurs qui influencent les attitudes et plus spécifiquement l’observance des mesures prescrites par les autorités. Des groupes de discussion et des entrevues individuelles semi-dirigées ont été réalisés en 2009 et 2010 au lac William, à la baie Missisquoi et au lac Roxton, auprès de différents groupes d’acteurs sociaux et illustrent que différentes représentations sociales du phénomène coexistent, et modulent le processus de gestion du risque. Cette étude montre l’intérêt d’aborder des phénomènes naturels tels que la prolifération des cyanobactéries en tant que construits socioculturels, car cette approche permet d’envisager les impacts liés à de tels phénomènes sous un angle différent et d’améliorer ainsi les interventions des gestionnaires afin de limiter ces impacts.Using a constructivist political ecology perspective, this exploratory qualitative research examines the social representations, attitudes and impacts that exist in relation to the phenomenon of cyanobacteria. Cyanobacteria are naturally occurring microorganisms found in most bodies of water ; certain species, especially when they are highly concentrated, release toxins that can pose a threat to population health. In Quebec, when the level of risk is considered serious, public health officials issue warnings concerning water-related activities and water consumption, but people do not always act in accordance with them. A qualitative study was undertaken with the aim of gaining a better understanding of the attitudes of citizens towards cyanobacteria and public health measures. It enabled us to identify both the meanings attached to this phenomenon – by drawing attention mainly on social representations of risk – and the other driving forces behind the attitudes and, in particular, towards compliance with measures prescribed by the authorities. Focus groups and semi-directed individual interviews involving several groups of social actors were conducted in 2009 and 2010 on Lake William, in the Missisquoi Bay and on Lake Roxton. Results illustrate coexistence of different social representations of the same phenomenon, which could modulate risk management process. This study points to the importance of considering natural phenomena such as the proliferation of cyanobacteria as socio-cultural constructs, because this approach can be applied to address the impacts of such phenomena from a different perspective and therefore improve management practices to reduce these impacts

    La prolifération des cyanobactéries au Québec : une perspective de sciences sociales sur le risque et la gestion

    No full text
    Using a constructivist political ecology perspective, this exploratory qualitative research examines the social representations, attitudes and impacts that exist in relation to the phenomenon of cyanobacteria. Cyanobacteria are naturally occurring microorganisms found in most bodies of water ; certain species, especially when they are highly concentrated, release toxins that can pose a threat to population health. In Quebec, when the level of risk is considered serious, public health officials issue warnings concerning water-related activities and water consumption, but people do not always act in accordance with them. A qualitative study was undertaken with the aim of gaining a better understanding of the attitudes of citizens towards cyanobacteria and public health measures. It enabled us to identify both the meanings attached to this phenomenon – by drawing attention mainly on social representations of risk – and the other driving forces behind the attitudes and, in particular, towards compliance with measures prescribed by the authorities. Focus groups and semi-directed individual interviews involving several groups of social actors were conducted in 2009 and 2010 on Lake William, in the Missisquoi Bay and on Lake Roxton. Results illustrate coexistence of different social representations of the same phenomenon, which could modulate risk management process. This study points to the importance of considering natural phenomena such as the proliferation of cyanobacteria as socio-cultural constructs, because this approach can be applied to address the impacts of such phenomena from a different perspective and therefore improve management practices to reduce these impacts

    Integrating agroforestry intercropping systems in contrasted agricultural landscapes : a SWOT-AHP analysis of stakeholders’ perceptions

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    Agroforestry intercropping systems have been developed as an alternative to conventional monocropping systems to address environmental, social and economic issues in a wide array of agricultural contexts. As research on the biological properties of these systems tends to demonstrate their potential, fostering their integration in agricultural landscapes requires an in-depth understanding of local stakeholders’ perceptions. Our study used the strengths, weaknesses, opportunities and threats approach in combination with the analytical hierarchy process (SWOT-AHP) to investigate the factors influencing local stakeholders’ decision to integrate agroforestry intercropping systems in two Regional County Municipalities and their perception of the relative suitability of three agroforestry intercropping system designs (crop-oriented, tree-oriented and landscape aesthetic-oriented). We conducted focus groups with farmers, farm and forestry advisors, urban planners and local authorities in a very intensive and a very extensive agricultural landscape in Quebec (Canada) and compared the results between stakeholders within and across the areas. Our results show that social factors seem to have more impact than biophysical factors on the decision to integrate agroforestry intercropping systems in intensive and extensive agricultural landscapes. The relative value given to the decision factors varies greatly across stakeholders’ categories and areas. Agroforestry intercropping systems designed to meet crop production needs or landscape aesthetic purposes are perceived as more suitable in both agricultural contexts than the tree-oriented design. Our results highlight crucial issues for agroforestry intercropping system deployment and the development of relevant agroforestry system designs through collective decision-making processes

    Une difficile prise en compte des changements sociaux en milieu minier nordique : le cas de Malartic (Québec)

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    En 2011, l’ouverture d’une mine d’or à ciel ouvert dans la municipalité de Malartic, en Abitibi-Témiscamingue, a suscité un éventail de changements sociaux. Le présent article décrit les impacts subis par les Malarticois entre 2006 et 2013, à partir des résultats d’un projet de recherche d’approche ethnographique au cours duquel des entretiens semi-dirigés ont été réalisés avec 93 acteurs du dossier. S’appuyant sur l’écologie politique et l’économie politique, l’analyse expose les principales limites des politiques publiques destinées à prendre en compte les impacts révélés par le cas de Malartic, et montre comment ces politiques s’inscrivent dans une logique néolibérale.In 2011, the opening of an open-pit gold mine in the municipality of Malartic in Abitibi-Témiscamingue (Quebec, Canada) triggered a range of social changes. This article, drawing on an ethnographic research project involving 93 semi-directed interviews, describes the changes experienced by the Malarticois between 2006 and 2013. With reference to political ecology and political economy, the analysis exposes the main limits of public policies intended to take into consideration the social impacts observed in the Malartic case and shows how these policies are part of a neo-liberal logic

    Striatal and Hippocampal Involvement in Motor Sequence Chunking Depends on the Learning Strategy

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    International audienceMotor sequences can be learned using an incremental approach by starting with a few elements and then adding more as training evolves (e.g., learning a piano piece); conversely, one can use a global approach and practice the whole sequence in every training session (e.g., shifting gears in an automobile). Yet, the neural correlates associated with such learning strategies in motor sequence learning remain largely unexplored to date. Here we used functional magnetic resonance imaging to measure the cerebral activity of individuals executing the same 8-element sequence after they completed a 4-days training regimen (2 sessions each day) following either a global or incremental strategy. A network comprised of striatal and fronto-parietal regions was engaged significantly regardless of the learning strategy, whereas the global training regimen led to additional cerebellar and temporal lobe recruitment. Analysis of chunking/grouping of sequence elements revealed a common prefrontal network in both conditions during the chunk initiation phase, whereas execution of chunk cores led to higher mediotemporal activity (involving the hippocampus) after global than incremental training. The novelty of our results relate to the recruitment of mediotemporal regions conditional of the learning strategy. Thus, the present findings may have clinical implications suggesting that the ability of patients with lesions to the medial temporal lobe to learn and consolidate new motor sequences may benefit from using an incremental strategy
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