834 research outputs found

    Regulation of Toxoplasma Motility by Calcium-Dependent Protein Kinases

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    Apicomplexans are protozoan parasites of animals, which must penetrate host cells to find a niche in which to replicate. To humans, they represent the most ubiquitous and deadliest eukaryotic pathogens, including Toxoplasma gondii and Plasmodium spp., the etiological agents of toxoplasmosis and malaria, respectively. A common mechanism enables these parasites to penetrate biological barriers and invade host cells actively, through a process termed gliding motility. This type of motility, unique to apicomplexans, relies on the directional translocation of adhesins via an actomyosin motor complex anchored in a vesicular network underlying the plasma membrane of the parasite. A variety of stimuli can trigger calcium increases in the parasite cytoplasm initiating motion, in part by regulating the secretion of adhesins from specialized organelles, called micronemes. Our studies investigate how these calcium signals are transduced to regulate T. gondii motility. Apicomplexans, like other chromalveolates and plants, possess calcium-dependent protein kinases: CDPKs) that are directly activated by calcium binding and have been proposed to participate in the transduction of calcium signals. A number of CDPKs are conserved among apicomplexans, and showed distinct subcellular localizations upon tagged expression in T. gondii, consistent with roles in different calcium-activated cellular pathways. Using a combination of chemical and genetic approaches we demonstrated that two of the conserved CDPKs are required for motility at different stages in the T. gondii life cycle. Generating a conditional knockout, we showed that TgCDPK1 is required for microneme secretion during egress and invasion. The essential role of this kinase was further supported through the use of bulky pyrazolo [3,4-d] pyrimidine: PP) analogues that inhibit TgCDPK1, and mirrored the effects of the conditional knockout. The specificity of these compounds is conferred by the expansion of the ATP-binding pocket in TgCDPK1 caused by the presence of a glycine at a key position called the `gatekeeper\u27, a feature unique among active parasite kinases. Mutating this residue to a methionine made TgCDPK1 resistant to the inhibitors, and enabled us to mutate the gatekeeper residue of a related kinase, TgCDPK3, rendering it sensitive to inhibition by PP analogues. This chemical-genetic strategy allowed us to implicate TgCDPK3 in the initiation of motility during egress, but demonstrate that its function is dispensable during invasion. Together, these observations provide the first evidence that related CDPKs regulate distinct signaling pathways, which distinguish the signaling events governing motility during egress and invasion by T. gondii. We also attempted to further understand the role of TgCDPK1 by examining its cellular targets. This process was also facilitated by the atypical ATP-binding pocket of TgCDPK1, which was able to bind bulky ATP analogues that allowed us to track its direct targets. This approach has allowed us to identify a number of putative TgCDPK1 targets. One such target, a dynamin-related protein, is phosphorylated in vivo in a CDPK1-dependent manner, consistent with a role in the regulation of motility. Together these observations provide a foundation for further characterization of CDPK signaling and the regulation of parasite motility. In particular, the chemical-genetic approaches adapted to parasites in these studies, represent a systematic means to dissecting these essential pathways in apicomplexans

    La khôra de los comunes: el rol de la comunidad local en dos paisajes productivos del Llobregat

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    En este artículo se parte de la metáfora de La Khôra de los Comunes para reflexionar, desde una nueva perspectiva, sobre el protagonismo de la comunidad local en la producción y preservación de dos paisajes productivos vinculados al río Llobregat. También se reflexiona sobre los cambios en la relación de agentes y paisaje condicionados por el contexto económico, social y urbanístico. Para comprender estos fenómenos se recurre al análisis comparativo de dos casos de estudio de ámbitos patrimoniales vinculados al río Llobregat, El Canal de la Infanta y El recinto industrial de Can Batlló. Se concluye el artículo con una síntesis de las distintas fases de la relación entre agentes y paisaje.The starting point of this article is The Khôra of the commons metaphor. First of all, we’ll discuss the role of local community in the design and preservation of two productive landscapes linked to Llobregat River. In addition, we analyse the relationship between agents and landscape that follows dynamics dependent of social, economic and urban context. To understand those phenomena two case studies are compared (Infanta canal and Can Batlló factory). In conclusion the paper synthetizes several periods common to both case studies, that explain the relationship between actors and landscape evolution

    Research study on the novel The Picture of Dorian Gray

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    Traballo fin de grao (UDC.FIL). Inglés: estudios lingüísticos y literarios. Curso 2012/201

    “She would never marry; one could not take her painting very seriously": A Feminist approach to Virginia Woolf’s To the Lighthouse

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    Traballo Fin de Grao en Lingua e Literatura Inglesas. Curso 2020-2021The title’s opening quote from Virginia Woolf’s To the Lighthouse (1927) illustrates not only the relationship between the two main women characters in the novel – Mrs Ramsay and Lily Briscoe – but also the existing tension between the patriarchal assumptions regarding the traditional roles of women in society and women’s artistic aspirations. In the novel these two characters are apparently presented as antagonists since they stand for contrasting models of femininity and have different outlooks on life. However, Woolf also undermines such opposition by emphasising how their relationship is based on mutual love and admiration for each other: “she [Briscoe] was and independent little creature and Mrs Ramsay liked her for it”. The aim of this work will be produce a critical analysis of Virginia Woolf’s modernist novel To the Lighthouse from a feminist perspective. Therefore, I will make a special emphasis on topics such as the role of the narrative’s female characters as well as the relationship between them, Woolf’s representation of both traditional roles of women and unconventional subjectivities in the novel, the relation between art and gender or the connection of this narrative with the author’s own experiences as a woman and as a writer. For this purpose, I will be using a range of critical works which comprise both primary sources, such as Virginia Woolf’s personal diaries, letters and essays, along with a selection of criticism which tackles nor only Woolf’s personal life but also To the Lighthouse in particular from a gender perspective

    Las formas de la cooperación: introducción a una metodología de análisis de los procesos cooperativos en la construcción del paisaje

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    Existen tantos paisajes como miradas sensibles al territorio. Esta investigación se aproxima al paisaje desde la perspectiva de la gobernanza y de los agentes que lo construyen. En este artículo se introduce una metodología de análisis que pretende establecer vínculos entre los procesos cooperativos, con los que algunas comunidades se adaptan al medio físico y social que habitan, y las formas del paisaje que resultan de ellos. En él confluyen dos líneas de trabajo: una deductiva, que plantea una serie de hipótesis teóricas generales; y otra inductiva, que pretende verificarlas desde lo particular. Para testar y afinar la metodología de trabajo, en esta ocasión se aplica a dos arquitecturas con un papel muy relevante en el relato de la industria textil vinculada al río Llobregat: la casa solariega Teixidor-Bassacs y la Torre del Amo de la colonia Viladomiu Nou.here are as many landscapes as sensitive approaches to the territory. This research looks to the landscape from the perspective of governance and stakeholders. This article is an introduction to an analysis methodology that seeks to stablish links between cooperative processes and landscape forms. Two work lines converge in the article: one deductive, which raises a series of general theoretical hypotheses; and another inductive, which tries to verify them looking to the specific. To nuance this method it is tested with two architectures with a relevant role in the story of the textile industry in the Llobregat River: the Teixidor-Bassacs house and the Viladomiu Nou owner’s house

    Arte Castrexa: escultura e decoración arquitectónica

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    Modeling a complex production line using virtual cells

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    This chapter presents modeling and simulation of a complex multistage multiproduct production line with four closed loop networks configuration, which also act as a virtual cell. This allows for a greater understanding of the functions within the production line through the simplification of the production flow with the addition of buffers between the cells. Virtual cells are crucial in this instance due to the dynamic configuration, which could help production system designers in optimizing the complex configuration of production
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