1,176 research outputs found
Exploration and characterization of the conoid complex in <i>Plasmodium falciparum</i> merozoites
No full textPlasmodium falciparum, the deadliest malaria parasite, poses a significant global health threat. Belonging to the Apicomplexa phylum, Plasmodium parasites have an apical complex crucial for motility and host cell invasion. The conoid, a dynamic organelle of elusive function composed of spiraling tubulin fibers, was previously thought to be lost in Plasmodium. Recent evidence from the host laboratory challenges this belief, identifying conoid complex proteins and an apical tubulin ring (ATR) in the ookinete stage responsible for colonizing the mosquito midgut. Preliminary investigations suggest a further reduction of the conoid complex at the merozoite stage, responsible for invading human red blood cells. This master’s thesis explores the conoid complex in P. falciparum merozoites, examining the expression of key components shared with other apicomplexan parasites, such as Myosin B (MyoB), double-cortin domain (DCX), and apical annuli protein 4 (AAP4). Using expansion microscopy (U-ExM), we confirm the expression of a conoid complex by observing a MyoB-GFP ring. However, no tubulin ring is observed, suggesting a reductive evolution of the conoid complex at the merozoite stage. In addition, we provide evidence that DCX plays an unexpected role in a distinct noninvasive stage that does not express a conoid. Generating a mixed population of PfAAP4-DiCre-HA parasites marked a significant step in understanding AAP4's role in the conoid complex. Our findings reveal that the conoid complex in P. falciparum merozoites is minimally conserved and that conoid proteins might be repurposed in non-invasive stages.Plasmodium falciparum, le parasite responsable du paludisme le plus mortel, représente une menace majeure pour la santé mondiale. En tant que membre du phylum des apicomplexes, les parasites Plasmodium possèdent un complexe apical essentiel pour leur mobilité et leur capacité à envahir les cellules hôtes. Le conoïde, une structure dynamique composée de fibres de tubuline en spirale, a une fonction encore peu connue. Bien que traditionnellement considéré comme perdu chez Plasmodium, les recherches menées par le laboratoire de Mathieu Brochet remettent en question cette notion en identifiant des protéines du complexe conoïde et un anneau de tubuline apical (ATR) au stade ookinète, qui est responsable de la colonisation de l'intestin du moustique. Des investigations préliminaires suggèrent une réduction supplémentaire du complexe conoïde au stade mérozoïte, responsable de l'invasion des globules rouges humains. Cette thèse de master explore le complexe conoïde chez les mérozoïtes de P. falciparum en examinant l'expression de composants clés partagés avec d'autres parasites apicomplexes, tels que la Myosine B (MyoB), le domaine double-cortine (DCX) et la protéine annulaire apicale 4 (AAP4). Nos expériences de microscopie d'expansion (U-ExM) confirment l'expression d'un complexe conoïde par l'observation d'un anneau MyoB-GFP. Cependant, aucun anneau de tubuline n'est observé, suggérant une évolution réductive du complexe conoïde au stade mérozoïte. De plus, nous apportons des preuves que DCX joue un rôle inattendu dans un stade non invasif distinct qui n'exprime pas de conoïde. La génération d'une population mixte de parasites PfAAP4-DiCre-HA constitue une avancée significative dans la compréhension du rôle de AAP4 dans le complexe conoïde. Nos résultats indiquent que le complexe conoïde chez les mérozoïtes de P. falciparum est conservé de manière minimale et que certaines protéines associées au conoïde pourraient être réaffectées dans des stades non invasifs du parasite
Analysis of Mathieu Equation Stable Solutions in the First Zone of Stability
No full textAbstractThe paper presents the results of a homogeneous Mathieu equation studies. Mathieu equation solutions are oscillations, modulated in amplitude and frequency. In the computational experiments we found dependences of the given oscillations on the ratio of the coefficients. These dependences are shown in graphs that can be used for an approximate estimation of the Mathieu equation solutions without integration
Pensar las escalas para pensar las luchas: Autor: Mathieu UHEL
No full textA través de un título sugerente, “pensar las escalas para pensar las luchas”, Mathieu Uhel entreteje la construcción teórico-crítica del concepto escala, generada por la geografía radical anglosajona de finales del siglo XX, con la necesidad/utilidad práctica de la escala para concienciar las luchas sociales. El artículo cumple un doble propósito: por un lado, delinear los elementos de lectura sobre el concepto escala; y, con ello, promover la atención de esta problemática en las luchas contemporáneas. En un primer apartado, Uhel ubica las discusiones académicas en torno a la escala, como herramienta metodológica útil para comprender la complejidad de las sociedades capitalistas; en el segundo apartado, el autor avanza la exposición en torno al contexto de la dimensión escalar del imperialismo capitalista; finalmente, el autor se centra en el rol de la actividad política a escala nacional en la tensa relación entre las imposiciones del capital y la lucha social.Por meio de um título sugestivo, “pensando escalas para pensar lutas”, Mathieu Uhel entrelaça a construção teórico-crítica do conceito de escala, gerado pela geografia radical anglo-saxônica do final do século XX, com a necessidade / utilidade prática escala para aumentar a consciência das lutas sociais. O artigo tem um duplo propósito: por um lado, delinear os elementos de leitura sobre o conceito de escala; e, com isso, promover atenção a esse problema nas lutas contemporâneas. Na primeira seção, Uhel localiza as discussões acadêmicas em torno da escala, como uma ferramenta metodológica útil para compreender a complexidade das sociedades capitalistas; na segunda seção, o autor avança a exposição em torno do contexto da dimensão escalar do imperialismo capitalista; por fim, o autor enfoca o papel da atividade política em escala nacional na tensa relação entre as imposições do capital e a luta social.Mathieu Uhel\u27s suggestive title, “Thinking about scales to think about struggles”, he interweaves the theoretical-critical construction of concept scale, generated by radical Anglo-Saxon geography in the late 20th century, with it´s practical utility to social struggles. The article serves two purposes: on the one hand, Uhel locates academic discussion around scale; and, with this, he promotes attention to this problem in contemporary struggles. In the first section, Uhel locates academic discussions around scale, as a useful methodological tool to understand the complexity of capitalist societies; in the second section, the author advances the argument around the context of the scalar dimension of capitalist imperialism; finally, the author focuses on the role of political activity on a national scale in the tense relationship between the impositions of capital and the social movement
Mathieu Ichou, Les Enfants d’immigrés à l’école
No full textIt is common to hear in the fields of educational and immigration sociology that on average, the children of immigrants do not perform as well in school as children of native-born parents. Mathieu Ichou offers an innovative sociological analysis on a topic that is heavily exploited by political and media discourse, and subject to much scientific controversy. The author takes distance from the homogenized vision of a “second generation” of students who have totally failed academically, and rep..
L'impatto dell'attività tintoria sull'ambiente. Firenze alla fine del Medioevo
No full textThe author aims to examine and categorize the range of dyeings materials used in the Florentine wool and silk textile industries in the late Middle Ages, focusing mainly on those produced within the regional space in order to evaluate the impact of the Florentine dyeing activity on the natural environment and the productive landscape of the Tuscan countryside. In particular, the author establishes a line of demarcation between cultivated and uncultivated resources in order to verify which constitutes an indication of the level of industrial development of medieval textile production. This further focuses on how the transition from the exploitation of wild resources to the exploitation of cultivated resources could reflect a greater degree of economic integration between the countryside and the city and contribute to the formation of a regional economic space
Mathieu de Fossey: su visión del mundo indígena mexicano
No full textThroughout these pages the author shows how Mathieu de Fossey perceived that it was not easy to make indigenous communities fit within the mould of the nation-state which, being based on the liberal and egualitarian ideology, was against the recognition of special regimes, such as those that created a peculiar status for the native population of the American territory during the period of Spanish colonial domination
Regulation of <i>Plasmodium</i> Gametogenesis
No full textMalaria is a major public health issue, responsible for 400 000 deaths every year. It is caused by Plasmodium parasites that circulate between vertebrate hosts and mosquito vectors. During this thesis, I focused on gametogenesis, a fascinating developmental stage to study Ca2+ signalling and regulation of the cell cycle in Plasmodium. Within seconds of activation, the cGMP- dependent protein kinase G (PKG) leads to mobilization of intracellular Ca2+. This is followed by a cascade of signalling events that in the male gametocyte regulates cell cycle progression to produce eight flagellated male gametes within ~10-12 minutes of the initial activation. I have identified a cGMP signalling platform involved in sensing extracellular cues activating gametogenesis and discovered a putative Ca2+ channel. Altogether my work sheds light into how Plasmodium transitions between host and vector and how it integrates and transduces cues from its environment to time its development.</p
Sensing extracellular cues via cGMP signaling in <i>Plasmodium</i> parasites
No full textMalaria remains a major public health problem despite significant eradication efforts, killing more than half a million people every year and putting nearly half the world’s population at risk. It is caused by unicellular eukaryotic Plasmodium parasites, which are transmitted via mosquito bites and replicate through a complex life cycle with several distinct stages involving both the vertebrate and the insect hosts.
During their life cycle, Plasmodium parasites must continually adapt to changing environments for successful proliferation and transmission. However, how they sense their surroundings to adapt their development remains a mystery, as they lack known receptors but can yet respond to extracellular signals.
In this thesis, I investigated how extracellular signals modulate cGMP homeostasis during transmission of Plasmodium gametocytes. Our findings show that a protein UGO (Unique GC Organizer) plays a crucial role in upregulating activity of the guanylyl cyclase GCα in response to extracellular cues. We also demonstrate that a signaling linking factor (SLF) is required for full basal GCα activity and optimal upregulation, and identified temperature-dependent epistatic interactions among two phosphodiesterases, PDEα and PDEδ.
Furthermore, we could show that premature activation of gametocytes at 37°C leads to abortive gametogenesis. A medium-throughput screening of approximately 4,000 compounds in P. berghei gametocytes identified several molecules capable of activating gametocytes by phenocopying XA mode of action, with the antidepressant sertraline showing particularly promising results. Interestingly, sertraline also shows a fast-killing activity against P. falciparum asexual blood stages in vitro. While the mode of action of sertraline in asexual blood stages remains to be identified, characterizing its target can pave the way for the development of novel multistage anti-Plasmodium molecules.</p
Mathieu de Fossey: su visión del mundo indígena mexicano
No full textÀ travers ces pages, l’auteur montre comment Mathieu de Fossey avait perçu la difficulté d’insérer le monde des communautés indigènes dans le moule d’un État national qui, accroché à une idéologie libérale égalitaire, refusait d’établir des régimes spéciaux comparables à ceux qui, durant la domination espagnole, avaient reconnu un statut particulier aux populations natives du continent américain.A través de estas páginas se muestra cómo Mathieu de Fossey percibió el difícil acoplamiento del mundo de las comunidades indígenas en el molde de un Estado nacional que, por estar sustentado en la ideología liberal igualitaria, era contrario al reconocimiento de regímenes especiales como los que, durante la dominación española, habían establecido un status peculiar para los aborígenes del territorio americano.Throughout these pages the author shows how Mathieu de Fossey perceived that it was not easy to make indigenous communities fit within the mould of the nation-state which, being based on the liberal and egualitarian ideology, was against the recognition of special regimes, such as those that created a peculiar status for the native population of the American territory during the period of Spanish colonial domination
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