Trypanosome Lytic Factor, an Antimicrobial High-Density Lipoprotein, Ameliorates Leishmania Infection

Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system

Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis

Blood coagulation starts immediately after damage to the vascular endothelium. This system is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the intrinsic coagulation pathway is not important for clotting in vivo, recent data obtained with genetically altered mice indicate that contact phase proteins seem to be essential for thrombus formation. We show that recombinant Ixodes ricinus contact phase inhibitor (Ir-CPI), a Kunitz-type protein expressed by the salivary glands of the tick Ixodes ricinus, specifically interacts with activated human contact phase factors (FXIIa, FXIa, and kallikrein) and prolongs the activated partial thromboplastin time (aPTT) in vitro. The effects of Ir-CPI were also examined in vivo using both venous and arterial thrombosis models. Intravenous administration of Ir-CPI in rats and mice caused a dose-dependent reduction in venous thrombus formation and revealed a defect in the formation of arterial occlusive thrombi. Moreover, mice injected with Ir-CPI are protected against collagen- and epinephrine-induced thromboembolism. Remarkably, the effective antithrombotic dose of Ir-CPI did not promote bleeding or impair blood coagulation parameters. To conclude, our results show that a contact phase inhibitor is an effective and safe antithrombotic agent in vivo

Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice

Trypanosoma brucei are extracellular protozoa transmitted to mammalian host by the tsetse fly. They developed several mechanisms that subvert host's immune defenses. Therefore analysis of genes affecting host's resistance to infection can reveal critical aspects of host-parasite interactions. Trypanosoma brucei brucei infects many animal species including livestock, with particularly severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to T. b. brucei. However, genes controlling susceptibility to this parasite have not been mapped. We analyzed the genetic control of survival after T. b. brucei infection using CcS/Dem recombinant congenic (RC) strains, each of which contains a different random set of 12.5% genes of their donor parental strain STS/A on the BALB/c genetic background. The RC strain CcS-11 is even more susceptible to parasites than BALB/c or STS/A. In F2 hybrids between BALB/c and CcS-11 we detected and mapped four loci, Tbbr1-4 (Trypanosoma brucei brucei response 1–4), that control survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have independent effects, Tbbr3 (chromosome 7) and Tbbr4 (chromosome 19) were detected by their mutual inter-genic interaction. Tbbr2 was precision mapped to a segment of 2.15 Mb that contains 26 genes

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Les friches culturelles, genèse d'un espace public de la culture

This study conserns ten different « cultural fallow » experiences (friche culturelle). It lies on questionnaires first, and then on a serial of interviews in situ about place, project, actors, actions and investment. The study considers the urban insertion and spatial quality ofthe places transformed in cultural spaces. The situations show thefield's diversityfor the analyse of a public expérience of culture. The making ofthe fallow form at a public euent enables to design a device to debate the cultural reason. The physical, material and symbolic conditions of social exchange constitue "cultural fallow" public spaces.L'étude concerne une dizaine de cas de figure différents d'expériences qui relèvent de ce que l'on désigne aujourd'hui sous le nom de friches culturelles. Elle s'appuie sur une enquête, menée par questionnaire d'abord, suivie par une série d'entretiens in situ, dont les thématiques sont celles du lieu, du projet, des acteurs, des actions et du financement. Considérés ici du point de vue de leur situation urbaine et à travers la qualité spatiale des lieux que les acteurs mobilisent (voire occupent) puis aménagent pour les transformer en « espaces culturels », les cas étudiés délimitent le terrain diversifié d'une analyse de la manière dont se structure une expérience publique de la culture. En s'attachant à la fabrication de la forme friche, à ce qui en fait un événement public, cette morphogenèse permet de dessiner les contours d'un dispositif de mise en débat de la raison culturelle. Les conditions physiques, matérielles et symboliques au sein desquelles se construisent les échanges dans le domaine de la culture sont constitutives de l'espace public de la culture que génèrent les friches culturelles.Esta investigación se refiere a diez experimentaciones acerca de lo que se llama en francés « friches culturelles », baldios urbanos, espacios convertidos por actores culturales. Se apoya sobre un cuestionario y entrevistas, cuyos temas son el lugar, el proyecto, los actores, el modo de finanzar. Por su situación en la cuidad, y el espacio que ocupan y transforman los actores para llegar a convertirles en espacios culturales, los casos estudiados delimitan el terreno donde se puede analizar la estructuración de una experiencia publica de la cultura. Nos interesamos a la fabricación del tipo « friche », que se vuelve en un acontecimiento publico, y que permite el debate sobre la razón cultural. Las « friches », baldios culturales, por las condiciones materiales y simbólicas de los intercambios que favorecen, con- truyen un espacio publico de cultura.Poggi Marie-Hélène, Vanhamme Marie. Les friches culturelles, genèse d'un espace public de la culture. In: Culture & Musées, n°4, 2004. Friches, squats et autres lieux : les nouveaux territoires de l'art ? (sous la direction de Emmanuelle Maunaye) pp. 37-55

Study of the reactivity of blast-furnace slag in cement

info:eu-repo/semantics/publishe

Reimagining marketing education – paradoxes marketing academics experience when introducing sustainability in the marketing curriculum

To improve sustainability education in marketing, sustainability needs to be included in the marketing curriculum in higher education. However, traditional, or mainstream, marketing courses do not usually actively encourage such topics. Marketing courses are still predominantly trapped in the dominant paradigm, ideology, centred around the need for continuous economic growth, consumption, and profits. This dominant logic still focusses mostly on material accumulation (Kemper et al, 2020). For making the shift to a sustainable society, a paradigm shift is required in the marketing curriculum in higher education because marketing students will be the marketing managers of tomorrow. Marketing scholars thus need to teach them how to incorporate sustainability in their future marketing decisions. As de Ruyter et al. (2022) mention, the very definition of effective marketing strategy needs to be reimagined; they call for the “facilitation of better marketing strategy that will boldly address society’s grand challenges” (p. 20). Studies have so far largely ignored issues related to the integration of sustainability in individual academic scholarship while academics in business schools are continuously confronted with tensions related to the continuous growth and profit-oriented ideology that business schools embody (Kemper et al. 2020). The purpose of this special session is to organize a discussion with the audience around the paradoxes and tensions marketing scholars experience when including sustainability in their courses, as well as how they do so and how they resolve (or not) the tensions. The objective of the special session is to better understand how marketing educators are bringing sustainability to the forefront of marketing education practices and are incorporating sustainability issues into course curriculum, pedagogical approaches, and discussions. The interactive session will start with two impulse presentations and continue with a discussion with the audience

La détention avant jugement au Canada

Objet de nombreuses réformes législatives, le recours à la détention avant jugement au Canada a connu au cours des dernières décennies une augmentation phénoménale. Définie par la privation de liberté d’une personne soupçonnée d’avoir commis un acte criminel mais non encore déclarée coupable, cette mesure soulève de nombreuses questions auxquelles cet ouvrage répond de façon nuancée et limpide. En conjuguant diverses sources de données, ce livre ancre la question de la détention avant jugement dans ses contextes scientifique, législatif et politique, et donne la parole aux différents acteurs de la chaîne pénale : policiers, procureurs, juges, avocats de la défense et justiciables détenus. Les auteures mettent ainsi en lumière les motifs et les mécanismes entourant l’usage de cet emprisonnement, tout en analysant le modèle judiciaire canadien. La réalité présentée ici est non seulement sujette à de multiples controverses, mais sa compréhension donne une clef pour appréhender les politiques et les pratiques pénales canadiennes actuelles

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae).

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.info:eu-repo/semantics/publishe