SARS-CoV-2 and Ebola: CHO-based manufacturing provides high quality subunit-vaccine candidates and diagnostics

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BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei

While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens

Dual Targeting of Antioxidant and Metabolic Enzymes to the Mitochondrion and the Apicoplast of Toxoplasma gondii

Toxoplasma gondii is an aerobic protozoan parasite that possesses mitochondrial antioxidant enzymes to safely dispose of oxygen radicals generated by cellular respiration and metabolism. As with most Apicomplexans, it also harbors a chloroplast-like organelle, the apicoplast, which hosts various biosynthetic pathways and requires antioxidant protection. Most apicoplast-resident proteins are encoded in the nuclear genome and are targeted to the organelle via a bipartite N-terminal targeting sequence. We show here that two antioxidant enzymes—a superoxide dismutase (TgSOD2) and a thioredoxin-dependent peroxidase (TgTPX1/2)—and an aconitase are dually targeted to both the apicoplast and the mitochondrion of T. gondii. In the case of TgSOD2, our results indicate that a single gene product is bimodally targeted due to an inconspicuous variation within the putative signal peptide of the organellar protein, which significantly alters its subcellular localization. Dual organellar targeting of proteins might occur frequently in Apicomplexans to serve important biological functions such as antioxidant protection and carbon metabolism

Presentación del libro: "Ínsulas Forasteras"

El libro que el lector tiene entre sus manos, Ínsulas forasteras. Canarias desde miradas ajenas, se gestó hace ya algunos años, cuando un grupo de compañeros de la Facultad de Filología de la Universidad de Las Palmas de Gran Canaria, los mismos que ahora somos —Victoria Galván González, José Ismael Gutiérrez, Ángeles Mateo del Pino, Francisco Quevedo García y Osvaldo Rodríguez Pérez—, decidimos llevar a cabo un trabajo de investigación, con el objetivo de presentarlo a la convocatoria de “Proyectos de Investigación sobre las relaciones entre Canarias-América 2002”, financiada por el Cabildo Insular de Gran Canaria a través de la Casa de Colón. Nuestra propuesta, que fue aceptada, se denominaba Invención de Canarias (Construcción literaria de un imaginario) y pretendía dar cuenta detallada de todos aquellos autores foráneos que a lo largo de los siglos hubieran recreado el espacio canario en sus escritos. Sin embargo, pronto nos percatamos de que la empresa resultaba demasiado ambiciosa, pues la nómina de escritores y obras de diversas épocas y geografías no hacía más que aumentar, lo que hacía imposible acotar el tema de estudio. Esto  nos llevó a revisar y a replantear nuestros primeros objetivos con el fin de profundizar en algunos aspectos que, en principio, no consideramos pertinentes. Es así que este volumen no sólo se ocupa de aquellos escritores de oficio, sino también de marineros, eclesiásticos, historiadores, hombres de acción, viajeros, botánicos, científicos… que han proyectado a Canarias en sus obras, casi a la misma vez que la han imaginado y construido. De ahí que nos haya interesado examinar no sólo la visión de aquellos que han pisado esta tierra, sino también de los que nunca la han visitado pero que, sin embargo, han elucubrado acerca de ella. Esta constante literaturización a través del tiempo es lo que nos ha conducido a analizar diversas formas literarias como la novela, el relato y la poesía, pero también otras escrituras como las crónicas, el diario o el ensayo. Para completar nuestro estudio consideramos oportuno ahondar en diversos conceptos, tales como en el de “imagen” y sus implicaciones a propósito de las representaciones sobre referentes reales o inventados, experimentados o fantaseados. O bien en el de “isla” y sus muchas connotaciones —míticas, psicológicas, literarias—. Pensamos que con ello podíamos ofrecer un recorrido por las múltiples interpretaciones con las que se ha recubierto a las islas a lo largo de la historia y cómo se ha configurado el arquetipo del topos insular para poder aplicarlo al archipiélago canario. Éste es otro de los aportes críticos que incorporamos a nuestro trabajo y que diferencia esta investigación de aquel primer proyecto

Erinnerung an W. Thielmann und Willingshausen

While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens

TERASENSE: THz device technology laboratory: final summary

The use of THz frequencies, particularly W and G band allows reaching higher resolution and deeper penetration in emerging applications like imaging, sensing, etc. The development of those new applications lays on reliable technologies, background of expertise and know-how. The CDS2008-00068 TERASENSE CONSOLIDER project has given the opportunity to extent upwards in frequency the previous background of the microwaves research group partners. This article summarizes the developments of the TERASENSE work package “THz Device Technology Laboratory”.This work was supported by the Spanish Ministerio de Ciencia e Innovación through the CONSOLIDER-INGENIO 2010 program reference CSD2008-00068 TERASENSE

TERASENSE: THz device technology laboratory

The use of THz frequencies, particularly W and G band allows reaching higher resolution and deeper penetration in emerging applications like imaging, sensing, etc. The development of those new applications lays on reliable technologies, background of expertise and know-how. The CDS2008-00068 TERASENSE CONSOLIDER project has given the opportunity to extent upwards in frequency the previous background of the microwaves research group partners. This article summarizes the developments of the TERASENSE work package “THz Device Technology Laboratory”

Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage

<p>Abstract</p> <p>Background</p> <p>The adhesion of <it>Plasmodium falciparum </it>parasitized red blood cell (PRBC) to human endothelial cells (EC) induces inflammatory processes, coagulation cascades, oxidative stress and apoptosis. These pathological processes are suspected to be responsible for the blood-brain-barrier and other organs' endothelial dysfunctions observed in fatal cases of malaria. Atorvastatin, a drug that belongs to the lowering cholesterol molecule family of statins, has been shown to ameliorate endothelial functions and is widely used in patients with cardiovascular disorders.</p> <p>Methods</p> <p>The effect of this compound on PRBC induced endothelial impairments was assessed using endothelial co-culture models.</p> <p>Results</p> <p>Atorvastatin pre-treatment of EC was found to reduce the expression of adhesion molecules and <it>P. falciparum </it>cytoadherence, to protect cells against PRBC-induced apoptosis and to enhance endothelial monolayer integrity during co-incubation with parasites.</p> <p>Conclusions</p> <p>These results might suggest a potential interest use of atorvastatin as a protective treatment to interfere with the pathophysiological cascades leading to severe malaria.</p

Analyse du rôle des molécules de transduction du signal dans la pathogenèse du neuropaludisme humain (application à l'identification de nouvelles cibles thérapeutiques)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF