Impaired Differentiation of Osteoclasts in TREM-2–deficient Individuals

TREM-2 is an immunoglobulin-like cell surface receptor associated with DAP12/KARAP that activates monocyte-derived dendritic cells (DCs) in vitro. Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease. This observation suggests that TREM-2 may function in myeloid cells other than DCs, most probably osteoclasts (OCs) and microglial cells, which are involved in bone modeling and brain function. Consistent with this prediction, here we show that OC differentiation is dramatically arrested in TREM-2–deficient patients, resulting in large aggregates of immature OCs that exhibit impaired bone resorptive activity. These results demonstrate a critical role for TREM-2 in the differentiation of mononuclear myeloid precursors into functional multinucleated OCs

REMICOM: Children´s reading comprehension monitoring assessment

La comprensión lectora es la capacidad para decodificar un texto, construir su sentido global y la representación mental del mismo. Para alcanzar una lectura comprensiva se ponen en juego un número importante de habilidades y conocimientos como el conocimiento del vocabulario, la generación de inferencias, el monitoreo de la comprensión y la comprensión de la estructura textual. La habilidad para monitorear la comprensión del proceso lector, o sea la habilidad que posee una persona para ir controlando su comprensión mientras lee, se considera de crucial importancia. El objetivo de este trabajo consistió en analizar las propiedades psicométricas (confiabilidad y validez) de un instrumento nuevo (Reviso Mi Comprensión, REMICOM) destinado a la evaluación de la habilidad de monitorear el estado de la lectura comprensiva en niños y niñas de 8 a 10 años, así como analizar las diferencias observadas entre los grados estudiados. Con este propósito se administró la prueba a 384 niños y niñas de 3º (8-9 años) y 4º (9-10 años) grados de escuela primaria, de nivel socioeconómico medio de Buenos Aires, Argentina. Las puntuaciones obtenidas mostraron evidencias satisfactorias de consistencia interna de los ítems y estabilidad temporal. Con respecto a las de validez, se obtuvo una correlación significativa con los resultados correspondientes a la comprensión lectora general, medidas por la Prueba de Comprensión Lectora de Complejidad Progresiva (CLP).A compreensão de leitura é a capacidade de decodificar um texto, construir seu significado global e sua representação mental. Para obter uma leitura abrangente, um número importante de habilidades e de conhecimentos são colocados em jogo como o conhecimento de vocabulário, geração de inferências, monitoramento da compreensão e entendimento da estrutura textual. Percebe-se que a capacidade de monitorar o entendimento do processo de leitura, ou seja, a capacidade de uma pessoa controlar seu entendimento durante a leitura é considerada crucial para atender a finalidade. Assim o objetivo desse estudo foi analisar as propriedades psicométricas (confiabilidade e validade) de um novo instrumento intitulado Reviso Mi Comprensión, REMICOM; e secundariamente avaliar a capacidade de monitorar o estado da leitura abrangente crianças de ambos os sexos (de 8 a 10 anos) e analisar as diferenças observadas entre os anos escolares estudados. O teste foi aplicado em 384 meninos e meninas do 3º (8-9 anos) e 4º (9-10 anos) ano do Ensino Fundamental e de nível socioeconômico médio da cidade de Buenos Aires, Argentina. Os escores obtidos mostraram evidências satisfatórias de consistência interna dos itens e de estabilidade temporal. Em relação a validade, obteve-se correlações significativasdo REMICOM com os resultados correspondentes à compreensão geral da leitura medidos pelo Teste de Compreensão da Complexidade Progressiva (CLP).La compréhension de la lecture est la capacité de décoder un texte, de construire sa signification globale et sa représentation mentale. Pour parvenir à une lecture complète, un nombre important de compétences et de connaissances sont mises en jeu, telles que la connaissance du vocabulaire, la génération d'inférences, le contrôle de la compréhension et la compréhension de la structure textuelle. La capacité de surveiller la compréhension du processus de lecture, c'est-à-dire la capacité d'une personne à contrôler sa compréhension pendant la lecture, est considérée comme d'une importance cruciale. L'objectif de ce travail était d'analyser les propriétés psychométriques (fiabilité et validité) d'un nouvel instrument (Reviso Mi Comprensión, REMICOM) visant à évaluer la capacité de surveiller l'état de lecture globale chez les garçons et les filles de 8 à 10 ans, ainsi que d'analyser les différences observées entre les grades étudiés. À cette fin, le test a été administré à 384 garçons et filles de 3e (8-9 ans) et 4e (9-10 ans) classes d'école primaire, de niveau socioéconomique moyen à Buenos Aires, Argentine. Les scores obtenus ont montré des preuves satisfaisantes de cohérence interne des items et de stabilité temporelle. Concernant ceux de la validité, une corrélation significative a été obtenue avec les résultats correspondant à la compréhension générale de la lecture, mesurés par le test de compréhension de la complexité de la lecture (CLP).Reading comprehension is the ability to decode a text, build its global meaning and its mental representation. To achieve a comprehensive reading, an important number of skills and knowledge are articulated, such as knowledge of vocabulary, generation of inferences, reading comprehension monitoring and understanding of the textual structure. The ability to monitor the understanding on the reading process, that is, the ability of a person to control their comprehension while reading, it´s considered of crucial importance. The aim of this research is to show the psychometric properties (of reliability and validity) of a new instrument aimed at assessing the ability of reading comprehension monitoring in children between 8 and 10 years old (Reviso Mi Comprensión -I Review My Understanding- , REMICOM), as well as analyze the differences observed between the school years studied. For this purpose, the test was administered to 384 boys and girls of 3rd (8-9 years old) and 4th (9-10 years old) courses of Primary school, of medium socioeconomic level in Buenos Aires, Argentina. The results obtained showed satisfactory evidence of internal consistency of the items and temporal stability. Concerning validity, a significant correlation was obtained with the results corresponding to the general reading comprehension measure, obtained by the Comprensión Lectora de Complejidad Progresiva test (CLP).Fil: Barreyro, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; ArgentinaFil: Musci, María Cecilia. Universidad Nacional del Comahue. Facultad de Ciencias de la Educación; ArgentinaFil: Buonsanti, Luciana. Indago. Equipo de Investigación Psicopedagógica.; ArgentinaFil: Brenlla, María Elena. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Psicología y Psicopedagogía. Centro de Investigaciones en Psicología y Psicopedagogía; ArgentinaFil: Gottheil, Barbara. Indago. Equipo de Investigación Psicopedagógica.; Argentin

REMICOM: children´s reading comprehension monitoring assessment

Resumen: La comprensión lectora es la capacidad para decodificar un texto, construir su sentido global y la representación mental del mismo. Para alcanzar una lectura comprensiva se ponen en juego un número importante de habilidades y conocimientos como el conocimiento del vocabulario, la generación de inferencias, el monitoreo de la comprensión y la comprensión de la estructura textual. La habilidad para monitorear la comprensión del proceso lector, o sea la habilidad que posee una persona para ir controlando su comprensión mientras lee, se considera de crucial importancia. El objetivo de este trabajo consistió en analizar las propiedades psicométricas (confiabilidad y validez) de un instrumento nuevo (Reviso Mi Comprensión, REMICOM) destinado a la evaluación de la habilidad de monitorear el estado de la lectura comprensiva en niños y niñas de 8 a 10 años, así como analizar las diferencias observadas entre los grados estudiados. Con este propósito se administró la prueba a 384 niños y niñas de 3º (8-9 años) y 4º (9-10 años) grados de escuela primaria, de nivel socioeconómico medio de Buenos Aires, Argentina. Las puntuaciones obtenidas mostraron evidencias satisfactorias de consistencia interna de los ítems y estabilidad temporal. Con respecto a las de validez, se obtuvo una correlación significativa con los resultados correspondientes a la comprensión lectora general, medidas por la Prueba de Comprensión Lectora de Complejidad Progresiva (CLP).Resumo: A compreensão de leitura é a capacidade de decodificar um texto, construir seu significado global e sua representação mental. Para obter uma leitura abrangente, um número importante de habilidades e de conhecimentos são colocados em jogo como o conhecimento de vocabulário, geração de inferências, monitoramento da compreensão e entendimento da estrutura textual. Percebe-se que a capacidade de monitorar o entendimento do processo de leitura, ou seja, a capacidade de uma pessoa controlar seu entendimento durante a leitura é considerada crucial para atender a finalidade. Assim o objetivo desse estudo foi analisar as propriedades psicométricas (confiabilidade e validade) de um novo instrumento intitulado Reviso Mi Comprensión, REMICOM; e secundariamente avaliar a capacidade de monitorar o estado da leitura abrangente crianças de ambos os sexos (de 8 a 10 anos) e analisar as diferenças observadas entre os anos escolares estudados. O teste foi aplicado em 384 meninos e meninas do 3º (8-9 anos) e 4º (9-10 anos) ano do Ensino Fundamental e de nível socioeconômico médio da cidade de Buenos Aires, Argentina. Os escores obtidos mostraram evidências satisfatórias de consistência interna dos itens e de estabilidade temporal. Em relação a validade, obteve-se correlações significativasdo REMICOM com os resultados correspondentes à compreensão geral da leitura medidos pelo Teste de Compreensão da Complexidade Progressiva (CLP).Résumé: La compréhension de la lecture est la capacité de décoder un texte, de construire sa signification globale et sa représentation mentale. Pour parvenir à une lecture complète, un nombre important de compétences et de connaissances sont mises en jeu, telles que la connaissance du vocabulaire, la génération d'inférences, le contrôle de la compréhension et la compréhension de la structure textuelle. La capacité de surveiller la compréhension du processus de lecture, c'est-à-dire la capacité d'une personne à contrôler sa compréhension pendant la lecture, est considérée comme d'une importance cruciale. L'objectif de ce travail était d'analyser les propriétés psychométriques (fiabilité et validité) d'un nouvel instrument (Reviso Mi Comprensión, REMICOM) visant à évaluer la capacité de surveiller l'état de lecture globale chez les garçons et les filles de 8 à 10 ans, ainsi que d'analyser les différences observées entre les grades étudiés. À cette fin, le test a été administré à 384 garçons et filles de 3e (8-9 ans) et 4e (9-10 ans) classes d'école primaire, de niveau socioéconomique moyen à Buenos Aires, Argentine. Les scores obtenus ont montré des preuves satisfaisantes de cohérence interne des items et de stabilité temporelle. Concernant ceux de la validité, une corrélation significative a été obtenue avec les résultats correspondant à la compréhension générale de la lecture, mesurés par le test de compréhension de la complexité de la lecture (CLP).Abstract: Reading comprehension is the ability to decode a text, build its global meaning and its mental representation. To achieve a comprehensive reading, an important number of skills and knowledge are articulated, such as knowledge of vocabulary, generation of inferences, reading comprehension monitoring and understanding of the textual structure. The ability to monitor the understanding on the reading process, that is, the ability of a person to control their comprehension while reading, it´s considered of crucial importance. The aim of this research is to show the psychometric properties (of reliability and validity) of a new instrument aimed at assessing the ability of reading comprehension monitoring in children between 8 and 10 years old (Reviso Mi Comprensión -I Review My Understanding- , REMICOM), as well as analyze the differences observed between the school years studied. For this purpose, the test was administered to 384 boys and girls of 3rd (8-9 years old) and 4th (9-10 years old) courses of Primary school, of medium socioeconomic level in Buenos Aires, Argentina. The results obtained showed satisfactory evidence of internal consistency of the items and temporal stability. Concerning validity, a significant correlation was obtained with the results corresponding to the general reading comprehension measure, obtained by the Comprensión Lectora de Complejidad Progresiva test (CLP)

In vivo characterization of the immune response towards the pathogenic Escherichia coli antigen SslE and modulation of the intestinal microbiota

International audienc

In vivo characterization of the mucosal immune response towards pathogenic Escherichia coli antigens and modulation of the intestinal microbiota

International audienc

Mixed mucosal-parenteral immunizations with the broadly conserved pathogenic Escherichia coli antigen SslE induce a robust mucosal and systemic immunity without affecting the murine intestinal microbiota

International audienceEmergence and dissemination of multidrug resistance among pathogenic Escherichia coli have posed a serious threat to public health across developing and developed countries. In combination with a flexible repertoire of virulence mechanisms, E. coli can cause a vast range of intestinal (InPEC) and extraintestinal (ExPEC) diseases but only a very limited number of antibiotics still remains effective against this pathogen. Hence, a broad spectrum E. coli vaccine could be a promising alternative to prevent the burden of such diseases, while offering the potential for covering against several InPEC and ExPEC at once. SslE, the Secreted and Surface-associated Lipoprotein of E. coli, is a widely distributed protein among InPEC and ExPEC. SslE functions ex vivo as a mucinase capable of degrading mucins and reaching the surface of mucus-producing epithelial cells. SslE was identified by reverse vaccinology as a protective vaccine candidate against an ExPEC murine model of sepsis, and further shown to be cross-effective against other ExPEC and InPEC models of infection. In this study, we aimed to gain insight into the immune response to antigen SslE and identify an immunization strategy suited to generate robust mucosal and systemic immune responses. We showed, by analyzing T cell and antibody responses, that mice immunized with SslE via an intranasal prime followed by two intramuscular boosts developed an enhanced overall immune response compared to either intranasal-only or intramuscular-only protocols. Importantly, we also report that this regimen of immunization did not impact the richness of the murine gut microbiota, and mice had a comparable cecal microbial composition, whether immunized with SslE or PBS. Collectively, our findings further support the use of SslE in future vaccination strategies to effectively target both InPEC and ExPEC while not perturbing the resident gut microbiota

Early upregulation of 18-kDa translocator protein in response to acute neurodegenerative damage in TREM2-deficient mice

Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD). We evaluated the effect of TREM2 deletion in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)–induced PD mouse model, measuring neurodegeneration and microglia activation using a combined in vivo imaging and postmortem molecular approach. In wild-type mice, MPTP administration induced a progressive decrease of [11C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and translocator protein (TSPO) transcript levels, [11C]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-α, Galectin-3, and Iba-1 (from day 1). In TREM2 null (TREM2−/−) mice, MPTP similarly affected neuron viability and microglial cells, as shown by the lower level of Iba-1 staining in basal condition, and reduced increment of Iba-1, TNF-α, and IL-1β in response to MPTP. Likely to compensate for TREM2 absence, TREM2−/− mice showed an earlier increment of [11C]PK11195 binding and a significant increase of IL-4. Taken together, our data demonstrate a central role of TREM2 in the regulation of microglia response to acute neurotoxic insults and suggest a potential modulatory role of TSPO in response to immune system deficit