3,675 research outputs found

    Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes

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    The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions

    The Astonishing Large Family of HSP40/DnaJ Proteins Existing in Leishmania

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    Abrupt environmental changes are faced by Leishmania parasites during transmission from a poikilothermic insect vector to a warm-blooded host. Adaptation to harsh environmental conditions, such as nutrient deprivation, hypoxia, oxidative stress and heat shock needs to be accomplished by rapid reconfiguration of gene expression and remodeling of protein interaction networks. Chaperones play a central role in the maintenance of cellular homeostasis, and they are responsible for crucial tasks such as correct folding of nascent proteins, protein translocation across different subcellular compartments, avoiding protein aggregates and elimination of damaged proteins. Nearly one percent of the gene content in the Leishmania genome corresponds to members of the HSP40 family, a group of proteins that assist HSP70s in a variety of cellular functions. Despite their expected relevance in the parasite biology and infectivity, little is known about their functions or partnership with the different Leishmania HSP70s. Here, we summarize the structural features of the 72 HSP40 proteins encoded in the Leishmania infantum genome and their classification into four categories. A review of proteomic data, together with orthology analyses, allow us to postulate cellular locations and possible functional roles for some of them. A detailed study of the members of this family would provide valuable information and opportunities for drug discovery and improvement of current treatments against leishmaniasis.This research was supported by the Spanish Ministerio de Ciencia, Innovación (MICINN), Agencia Estatal de Investigación (AEI), grant number PID2020-117916RB-I00, and Instituto de Salud Carlos III, grant CB21/13/00018 (CIBERINFEC). An institutional grant from Fundacion Ramon Areces is also acknowledged.S

    Propriedades psicométricas do Questionário Revisado de Bullying/Vitimização de Olweus para Crianças em español

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    Bullying is an important risk factor for the mental health of children and adolescents, since victim’s present higher levels of emotional problems while those who carry it out show greater behavioural problems. Despite its relevance, few instruments exist for its measurement in school-age children. The present study sought to evaluate the psychometric properties of the Revised Olweus Bully/Victim Questionnaire in a Spanish-speaking sample, with the particularity of being the first analysis of Spanish-speaking children. A quantitative study was carried out, implementing AFE, AFC, and Spearman's correlations. An intentional sample of 670 Argentinian children, male (48 %) and female (52 %), from 10 to 12 years old (mean age= 10.80; SD = 0.72) answered this test, such as the Friendship Quality Scale and the Kovacs Depression Inventory. The results indicated a factorial structure of two dimensions called victimization and bullying that coincided with those postulated by the author of the questionnaire. Cronbach's and Omega's alphas were satisfactory. The evidence of concurrent validity with the perception of the quality of friendship and depression was confirmed. The results indicated that this questionnaire presented adequate psychometric properties in its adaptation to Argentinian Spanish.El bullying es un importante factor de riesgo para la salud mental de niños y adolescentes, ya que las víctimas presentan mayores niveles de problemas emocionales; mientras que los acosadores muestran mayores problemas de conducta. A pesar de su relevancia, existen pocos instrumentos para su medición en niños de edad escolar. El presente estudio buscó evaluar las propiedades psicométricas del Cuestionario Revisado de Bullying/Victimización de Olweus en una muestra de habla hispana, con la particularidad de ser el primer análisis de habla hispana en niños. Se realizó un estudio instrumental, implementando AFE, AFC y correlaciones de Pearson. Una muestra intencional de 670 niños argentinos, varones (48 %) y mujeres (52 %), de 10 a 12 años (edad media = 10.80; DE = .72) contestaron el cuestionario, la Escala de Calidad de la Amistad y el Inventario de Depresión de Kovacs. Los resultados indicaron una estructura factorial de dos dimensiones: victimización y bullying, que coincidieron con las postuladas por el autor del cuestionario. Los valores de los coeficientes alfas de Cronbach y de omega de McDonald fueron satisfactorios. Se confirmó la evidencia de validez concurrente con la percepción de la calidad de la amistad y la depresión. El cuestionario presentó adecuadas propiedades psicométricas en su adaptación al español argentino.  O bullying é um importante fator de risco para a saúde mental de crianças e adolescentes, uma vez que as vítimas apresentam maiores níveis de problemas emocionais enquanto aqueles que o praticam apresentam maiores problemas comportamentais. Apesar de sua relevância, existem poucos instrumentos para sua mensuração em crianças em idade escolar. O presente estudo procurou avaliar as propriedades psicométricas do Questionário Revisado de Bullying/ Vitimização de Olweus em uma amostra de língua espanhol, com a particularidade de ser a primeira análise em língua espanhola em crianças. Foi realizado um estudo instrumental, implementando AFE, AFC e correlações de Pearson. Uma amostra intencional de 670 crianças argentinas, meninos (48 %) e meninas (52 %), com idades de 10 a 12 anos (média de idade = 10,80; DP = 0,72) responderam ao questionário, a Escala de Qualidade da Amizade e o Inventário de Depressão de Kovacs. Os resultados indicaram uma estrutura fatorial de duas dimensões denominadas vitimização e bullying, que coincidiram com as postuladas pelo autor do questionário. Os valores dos coeficientes alfas de Cronbach e Omega de McDonald foram satisfatórios. Foi confirmada a evidência de validade concorrente com a qualidade percebida da amizade e a depressão. O questionário apresentou propriedades psicométricas adequadas em sua adaptação ao espanhol argentino
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