RESUMEN
In vitro models of autoimmunity are constrained by an inability to culture affected epithelium alongside the complex tissue-resident immune microenvironment. Coeliac disease (CeD) is an autoimmune disease in which dietary gluten-derived peptides bind to the major histocompatibility complex (MHC) class II human leukocyte antigen molecules (HLA)-DQ2 or HLA-DQ8 to initiate immune-mediated duodenal mucosal injury1-4. Here, we generated air-liquid interface (ALI) duodenal organoids from intact fragments of endoscopic biopsies that preserve epithelium alongside native mesenchyme and tissue-resident immune cells as a unit without requiring reconstitution. The immune diversity of ALI organoids spanned T cells, B and plasma cells, natural killer (NK) cells and myeloid cells, with extensive T-cell and B-cell receptor repertoires. HLA-DQ2.5-restricted gluten peptides selectively instigated epithelial destruction in HLA-DQ2.5-expressing organoids derived from CeD patients, and this was antagonized by blocking MHC-II or NKG2C/D. Gluten epitopes stimulated a CeD organoid immune network response in lymphoid and myeloid subsets alongside anti-transglutaminase 2 (TG2) autoantibody production. Functional studies in CeD organoids revealed that interleukin-7 (IL-7) is a gluten-inducible pathogenic modulator that regulates CD8+ T-cell NKG2C/D expression and is necessary and sufficient for epithelial destruction. Furthermore, endogenous IL-7 was markedly upregulated in patient biopsies from active CeD compared with remission disease from gluten-free diets, predominantly in lamina propria mesenchyme. By preserving the epithelium alongside diverse immune populations, this human in vitro CeD model recapitulates gluten-dependent pathology, enables mechanistic investigation and establishes a proof of principle for the organoid modelling of autoimmunity.
Asunto(s)
Enfermedad Celíaca , Duodeno , Interleucina-7 , Mucosa Intestinal , Modelos Biológicos , Organoides , Humanos , Autoanticuerpos/inmunología , Autoinmunidad , Linfocitos B/inmunología , Linfocitos B/metabolismo , Biopsia , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/patología , Enfermedad Celíaca/metabolismo , Duodeno/inmunología , Duodeno/patología , Duodeno/metabolismo , Epítopos/inmunología , Glútenes/inmunología , Glútenes/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/inmunología , Antígenos HLA-DQ/inmunología , Antígenos HLA-DQ/metabolismo , Interleucina-7/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Células Asesinas Naturales/inmunología , Células Mieloides/inmunología , Organoides/inmunología , Organoides/metabolismo , Organoides/patología , Proteína Glutamina Gamma Glutamiltransferasa 2/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of KRT5+ cells in basal organoids revealed a distinct population of ITGA6+ITGB4+ mitotic cells, whose offspring further segregated into a TNFRSF12Ahi subfraction that comprised about ten per cent of KRT5+ basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia.
Asunto(s)
COVID-19/virología , Pulmón/citología , Modelos Biológicos , Organoides/citología , Organoides/virología , SARS-CoV-2/fisiología , Técnicas de Cultivo de Tejidos , Células Epiteliales Alveolares/citología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/virología , COVID-19/metabolismo , COVID-19/patología , Diferenciación Celular , División Celular , Células Clonales/citología , Células Clonales/metabolismo , Células Clonales/virología , Humanos , Técnicas In Vitro , Subtipo H1N1 del Virus de la Influenza A/crecimiento & desarrollo , Subtipo H1N1 del Virus de la Influenza A/fisiología , Integrina alfa6/análisis , Integrina beta4/análisis , Queratina-5/análisis , Organoides/metabolismo , Neumonía Viral/metabolismo , Neumonía Viral/patología , Neumonía Viral/virología , SARS-CoV-2/crecimiento & desarrollo , Análisis de la Célula Individual , Receptor de TWEAK/análisisRESUMEN
Preschool teachers' perceptions about relationships with students (teacher-child relationships [TCRs]) predict children's subsequent social competence (SC) and academic progress. Why this is so remains unclear. Do TCRs shape children's development, or do child attributes influence both TCRs and subsequent development? Relations between TCRs and other measures were examined for 185 preschoolers (107 girls, 89 longitudinal, and ~75% European American). Teachers rated TCRs and child social/affective behaviors. Teacher-child interactions (TCIs) and children's affect expressiveness were observed. Child SC and receptive vocabulary were assessed. TCRs were significantly correlated with each type of outcome. TCIs, SC, expressed affect, and teacher-rated behaviors also predicted TCRs longitudinally. Results suggest that TCR ratings predict subsequent adaptation because they summarize children's behavioral profiles rather than on TCR quality per se.
Asunto(s)
Relaciones Interpersonales , Maestros , Femenino , Humanos , Preescolar , Maestros/psicología , Conducta Social , Estudiantes/psicología , Receptores de Antígenos de Linfocitos TRESUMEN
The synthesis and investigation of the physicochemical properties of a novel one-dimensional (1D) hybrid organic-inorganic perovskitoid templated by the 1,1,1-trimethylhydrazinium (Me3Hy+) cation are reported. (Me3Hy)[PbI3] crystallizes in the hexagonal P63/m symmetry and undergoes two phase transitions (PTs) during heating (cooling) at 322 (320) and 207 (202) K. X-ray diffraction data and temperature-dependent vibrational studies show that the second-order PT to the high-temperature hexagonal P63/mmc phase is associated with a weak change in entropy and is related to weak structural changes and different confinement of cations in the available space. The second PT to the low-temperature orthorhombic Pbca phase that corresponds to the high change in entropy and dielectric switching is associated with an ordering of the trimethylhydrazinium cations, re-arrangement and strengthening of hydrogen bonds, and slightly shifted lead-iodide octahedral chains. The high-pressure Raman data revealed two additional PTs, one between 2.8 and 3.2 GPa, related to the symmetry decrease, ordering of the cations, and inorganic chain distortion, and the other in the 6.4-6.8 GPa range related to the partial and reversible amorphization. Optical studies revealed that (Me3Hy)[PbI3] has a wide band gap (3.20 eV) and emits reddish-orange excitonic emission at low temperatures with an activation energy of 65 meV.
RESUMEN
In this work, a simple, fast and dry method for the fabrication of a thermochromic product with a high load of VO2 (M1) consisting of the controlled heat treatment of pure vanadium nanoparticles in air is presented. After a complete design of experiments, it is concluded that the most direct way to attain the maximum transformation of V into VO2 (M1) consists of one cycle with a fast heating ramp of 42 °C s-1 , followed by keeping 700 °C for 530-600â seconds, and a subsequent cooling at 0.05 °C s-1 . Careful examination of these results lead to a second optimum, even more suitable for industrial production (quicker and less energy-intensive because of its lower temperatures and shorter times), consisting of subjecting V to two consecutive cycles of temperatures and times (625 °C for 5â minutes) with similar preheating (42 °C s-1 ) but a much faster postcooling (â¼ 8 °C s-1 ). These green reactions only use the power for heating a tube open to atmosphere and a vanadium precursor; without assistance of reactive gases or catalysts, and no special vacuum or pressure requirements. The best products present similar thermochromic properties but higher thermal stability than commercial VO2 particles. These methods can be combined with VO2 doping.
RESUMEN
Adolescents' dyadic relationships are likely influenced by the cultural context within which they exist. This study applied a person-oriented approach to examine how perceived support and negativity were manifested across youths' relationships with mothers, fathers, and best friends, simultaneously, and how distinct relationship profiles were linked to adaptive and maladaptive functioning (aggression, anxious-withdrawal, prosociality) within and across cultures. Participants resided in metropolitan areas of South Korea, the United States, and Portugal (10-14 years; N = 1,233). Latent profile analyses identified relationship profiles that were culturally common or specific. Additional findings highlighted commonality in the relations between a high-quality relationship profile and adaptive functioning, as well as cultural specificity in the buffering and differential effects of distinct relationship profiles on social-behavioral outcomes.
Asunto(s)
Amigos , Madres , Adolescente , Comparación Transcultural , Padre , Femenino , Humanos , Relaciones Interpersonales , Masculino , Ajuste Social , Estados UnidosRESUMEN
Comparative psychology provides important contributions to our understanding of the origins of human language. The presence of common features in human and nonhuman primate communication can be used to suggest the evolutionary trajectories of potential precursors to language. However, to do so effectively, our findings must be comparable across diverse species. This systematic review describes the current landscape of data available from studies of gestural communication in human and nonhuman primates that make an explicit connection to language evolution. We found a similar number of studies on human and nonhuman primates, but that very few studies included data from more than one species. As a result, evolutionary inferences remain restricted to comparison across studies. We identify areas of focus, bias, and apparent gaps within the field. Different domains have been studied in human and nonhuman primates, with relatively few nonhuman primate studies of ontogeny and relatively few human studies of gesture form. Diversity in focus, methods, and socio-ecological context fill important gaps and provide nuanced understanding, but only where the source of any difference between studies is transparent. Many studies provide some definition for their use of gesture; but definitions of gesture, and in particular, criteria for intentional use, are absent in the majority of human studies. We find systematic differences between human and nonhuman primate studies in the research scope, incorporation of other modalities, research setting, and study design. We highlight eight particular areas in a call to action through which we can strengthen our ability to investigate gestural communication's contribution within the evolutionary roots of human language.
Asunto(s)
Gestos , Lenguaje , Comunicación Animal , Animales , PrimatesRESUMEN
We examine the factorial structure of the Security Scale Questionnaire (SSQ), exploring measurement invariance across mother-father-child attachment relationships, child sex, and country. We used the new 21-item SSQ version that integrates both safe haven and secure base behaviors in a two factors structure. Participants were 457 children (224 girls and 233 boys), ranging from 9 to 14 years old (M = 10.84, SD = 1.02) from Portuguese and USA samples. We confirmed the SSQ's two-factor structure, although four items were unrelated to the latent structure and excluded from the final model. Results showed that SSQ can be used to study both mother/child and father/child attachment relationships. Multi-group analyses suggested measurement invariance between boys and girls and between Portuguese and USA samples. Our findings suggest that the SSQ can be considered a valid and cost-effective tool to measure perceived attachment security in middle childhood for both mother/child and father/child relationships.
Asunto(s)
Padre , Madres , Adolescente , Niño , Relaciones Padre-Hijo , Femenino , Humanos , Masculino , Relaciones Madre-Hijo , Apego a ObjetosRESUMEN
High and stable behavioral inhibition during early childhood is a risk factor for later anxiety disorders. The few available interventions targeted at behavioral inhibition have not yet been implemented in European countries. Evaluating intervention acceptability is essential when introducing interventions in new cultures. This study aimed to explore the perceptions of parents about the acceptability of the multicomponent Turtle Program in Portugal. Participants were 12 parents (from seven families) of children with a positive screening on the Behavioral Inhibition Questionnaire and no diagnoses of developmental disorders/selective mutism. Children's mean age was 55.86 months and most children were female and first-born. Parents and children participated in the eight-sessions Turtle Program. After each session, parents completed weekly satisfaction checklists. Following completion of the full intervention, parents were invited to participate in individual qualitative in-depth interviews. The thematic analysis revealed that both parents perceived the intervention objectives and contents as relevant. Both parents suggested the introduction of follow-up sessions, the discussion of practical experiences, the need to be sensitive to cultural differences in positive language, and the provision of more feedback about children's activities. These findings support prior research on the acceptability and cultural tailoring needed for parenting and child socioemotional learning interventions.
Una alta y estable conducta de inhibición durante la temprana niñez es un factor de riesgo para posteriores trastornos de ansiedad. Las pocas intervenciones disponibles que se enfocan en la inhibición de la conducta no se han implementado aún en países europeos. Evaluar el nivel de aceptación de la intervención es esencial cuando las intervenciones se introducen en nuevas culturas. Este estudio se propuso explorar las percepciones de los progenitores acerca del nivel de aceptación del multi-compuesto Programa Tortuga en Portugal. Los participantes fueron 12 progenitores (de siete familias) de niños con una positiva detección en el Cuestionario de Inhibición de la Conducta y sin diagnóstico de trastornos de desarrollo/mutismo selectivo. La edad promedio de los niños fue 55.86 meses y la mayoría eran niñas y primogénitas. Los progenitores y los niños participaron en las ocho sesiones del Programa Tortuga. Después de cada sesión, los progenitores completaron listas semanales de chequeo de la satisfacción. Luego de completar la intervención en su totalidad, se invitó a los progenitores a participar en entrevistas cualitativas individuales para profundizar. Los análisis temáticos revelaron que ambos progenitores percibieron como relevantes los objetivos y el contenido de la intervención. Ambos progenitores sugirieron introducir sesiones de seguimiento, la discusión de experiencias prácticas, la necesidad de mostrarse sensible a las diferencias culturales en lenguaje positivo y la provisión de más información sobre las actividades de los niños. Estos resultados apoyan la investigación anterior sobre el nivel de aceptación y la adaptación cultural necesarias en las intervenciones sobre la crianza y el aprendizaje socioemocional del niño.
L'inhibition comportementale élevée et stable durant la petite enfance est un facteur de risque pour des troubles de l'anxiété plus tard. Quelques interventions disponibles ciblant l'inhibition comportementale n'ont pas encore été mises en Åuvre dans les pays européens. Evaluer l'acceptabilité de l'intervention est essentiel lorsqu'on introduit des interventions dans de nouvelles cultures. Cette étude s'est donnée pour but d'explorer les perceptions des parents à propos de l'acceptabilité du Programme Tortue à composants multiples au Portugal. Les participants ont consisté en 12 parents (de sept familles) d'enfants ayant eu un dépistage positif au Questionnaire d'Inhibition Comportementale et aucun diagnostic de troubles développementaux / mutisme sélectif. L'âge moyen des enfants était de 55,86 mois et la plupart des enfants étaient des filles et des premières nées. Les parents et les enfants ont participé au Programme Tortue de huit séances. Après chaque séance les parents ont rempli des checklists de satisfaction hebdomadaires. Après avoir terminé l'intervention totale les parents ont été invité à participer à des entretiens individuels en profondeur et qualitatifs. L'analyse thématique a révélé que les deux parents percevaient les objectifs d'intervention et les contenus comme étant pertinents. Les deux parents ont suggéré l'introduction de séances de suivi, la discussion d'expériences pratiques, le besoin d'être sensible aux différences culturelles dans le langage positif et le besoin de plus de commentaires sur les activités des enfants. Ces résultats soutiennent les recherches précédentes sur l'acceptabilité et l'adaptation culturelle nécessaire pour le parentage et les interventions pour le développement socioémotionnel de l'enfant.
Asunto(s)
Lenguaje , Padres , Preescolar , Femenino , Humanos , Responsabilidad Parental , Percepción , PortugalRESUMEN
The main goal of this study was to explore the contributions of early father-child and mother-child attachment relationships to children's later social competence with their preschool peers; possible unique and shared contributions were tested. Using a multi-method design and focusing on direct observation, attachment was assessed at home at age 3 with the Attachment Behavior Q-sort (AQS) and two years later social competence was assessed at classrooms of 5-year-olds using a set of seven measurement indicators that are part of the Hierarchical Model of Social Competence. Results show that attachment to each parent made unique and significant contributions to children's social competence and suggested the possibility that each caregiver may have somewhat different patterns of influence on the different indicators of children's social competence. Findings also suggest the possibility that a secure attachment with one parent may buffer the impact of having an insecure relationship with the other. Due to sample size, these results should be seen as a starting point to generate new and larger studies.
Asunto(s)
Relaciones Padre-Hijo , Relaciones Madre-Hijo/psicología , Apego a Objetos , Habilidades Sociales , Adulto , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Recent meta-analyses have reported significant effects of attachment quality on social competence, mostly using observational assessments of attachment behavior to assess security. We analyze the associations between attachment security - assessed as a secure base script, and social competence with peers - measured by teachers' ratings on two self-report instruments, in a Portuguese sample of 82 preschool children (34 boys and 48 girls). We also tested the association between children's secure base script scores and teacher ratings for externalizing and internalizing symptomatology. Results show significant sex differences. Girls had higher scores on secure base script and were rated by teachers as more socially competent, while boys received higher ratings for aggressive/externalizing behaviors. Nonetheless, when the effect of child sex was controlled, attachment representations were positively associated with child social competence and negatively associated with ratings of externalizing behaviors.
Asunto(s)
Conducta Infantil/psicología , Maestros , Habilidades Sociales , Adulto , Niño , Preescolar , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Narración , Observación , Relaciones Padres-Hijo , Grupo Paritario , Portugal , Análisis y Desempeño de TareasRESUMEN
Peer victimization is one of the most prominent problems during adolescence. Research has distinguished aggressive and non-aggressive victims; however, there are still significant drawbacks in understanding the social and family functioning of these different groups of victimized adolescents. This study aimed to compare social behavior and perceived attachment security to parents of Portuguese adolescents, classified as aggressive victims, non-aggressive victims and non-victims. The sample consisted of 222 adolescents (115 boys, 107 girls) who completed the Kerns Security Scale and the Extended Class Play, to assess perceived attachment security and social behavior, respectively. Controlling for age and sex, aggressive victims and non-aggressive victims differed in anxious withdrawal but shared a similar profile in peer exclusion and prosocial behavior. Only aggressive victims reported lower attachment security to mother and father when compared to non-victims. These findings underline that victimized adolescents constitute a heterogeneous group in terms of their social and family functioning.
Asunto(s)
Conducta del Adolescente/psicología , Agresión/psicología , Víctimas de Crimen/psicología , Apego a Objetos , Relaciones Padres-Hijo , Adolescente , Estudios Transversales , Familia/psicología , Femenino , Humanos , Masculino , Grupo Paritario , Percepción , Portugal , Encuestas y CuestionariosRESUMEN
Several bacterial pathogens and viruses interfere with the cell cycle of their host cells to enhance virulence. This is especially apparent in bacteria that colonize the gut epithelium, where inhibition of the cell cycle of infected cells enhances the intestinal colonization. We found that intracellular Salmonella enterica serovar Typhimurium induced the binucleation of a large proportion of epithelial cells by 14 h postinvasion and that the effect was dependent on an intact Salmonella pathogenicity island 2 (SPI-2) type 3 secretion system. The SPI-2 effectors SseF and SseG were required to induce binucleation. SseF and SseG are known to maintain microcolonies of Salmonella-containing vacuoles close to the microtubule organizing center of infected epithelial cells. During host cell division, these clustered microcolonies prevented the correct localization of members of the chromosomal passenger complex and mitotic kinesin-like protein 1 and consequently prevented cytokinesis. Tetraploidy, arising from a cytokinesis defect, is known to have a deleterious effect on subsequent cell divisions, resulting in either chromosomal instabilities or cell cycle arrest. In infected mice, proliferation of small intestinal epithelial cells was compromised in an SseF/SseG-dependent manner, suggesting that cytokinesis failure caused by S Typhimurium delays epithelial cell turnover in the intestine.
Asunto(s)
Citocinesis , Interacciones Huésped-Patógeno , Salmonella typhimurium/fisiología , Animales , Ciclo Celular , Proliferación Celular , Femenino , Intestino Delgado/microbiología , Intestino Delgado/patología , Ratones , Infecciones por Salmonella/metabolismo , Infecciones por Salmonella/microbiología , Sistemas de Secreción Tipo III/metabolismoRESUMEN
Cell surface-exposed cholesterol is crucial for cell attachment and invasion of many viruses and bacteria, including the bacterium Salmonella, which causes typhoid fever and gastroenteritis. Using flow cytometry and 3D confocal fluorescence microscopy, we found that mitotic cells, although representing only 1-4% of an exponentially growing population, were much more efficiently targeted for invasion by Salmonella. This targeting was not dependent on the spherical shape of mitotic cells, but was instead SipB and cholesterol dependent. Thus, we measured the levels of plasma membrane and cell surface cholesterol throughout the cell cycle using, respectively, brief staining with filipin and a fluorescent ester of polyethylene glycol-cholesterol that cannot flip through the plasma membrane, and found that both were maximal during mitosis. This increase was due not only to the rise in global cell cholesterol levels along the cell cycle but also to a transient loss in cholesterol asymmetry at the plasma membrane during mitosis. We measured that cholesterol, but not phosphatidylserine, changed from a â¼2080 outerinner leaflet repartition during interphase to â¼5050 during metaphase, suggesting this was specific to cholesterol and not due to a broad change of lipid asymmetry during metaphase. This explains the increase in outer surface levels that make dividing cells more susceptible to Salmonella invasion and perhaps to other viruses and bacteria entering cells in a cholesterol-dependent manner. The change in cholesterol partitioning also favoured the recruitment of activated ERM (Ezrin, Radixin, Moesin) proteins at the plasma membrane and thus supported mitotic cell rounding.
Asunto(s)
Membrana Celular/metabolismo , Colesterol/metabolismo , Células Epiteliales/fisiología , Metafase , Salmonella typhimurium/patogenicidad , Proteínas Bacterianas/metabolismo , Procesos de Crecimiento Celular , Proteínas del Citoesqueleto/metabolismo , Células Epiteliales/microbiología , Citometría de Flujo , Gastroenteritis/microbiología , Células HeLa , Interacciones Huésped-Patógeno , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de Microfilamentos/metabolismo , Microscopía Confocal , VirulenciaRESUMEN
The present study aims to test Bowlby's suggestions concerning relations between the child's attachment quality with parents and subsequently constructed models of self-worth during early childhood. In most research on this question, attachment with mothers is considered in relation to self-worth but the child's attachment with fathers is not. Neither has the peer group been studied as an influence on child self-esteem, in the context of attachment research. This study addresses these relatively unstudied influences on child self-esteem. Attachment security to mother and father was measured by the Attachment Behavior Q-Set at two and half years of age. At five years of age social acceptance was measured using two sociometric techniques, and the self-esteem with the California Child Q-Sort. Our analyses indicated that security of the attachment to father and peer acceptance are both unique, significant predictors of the childrens' self-esteem. The security of the attachment to mother was also related to child self-esteem but did not emerge as a uniquely significant predictor. Peer acceptance appeared to moderate of the effect of the security of the attachment to father on the self-esteem of children. Our results extend the relatively sparse literature relating early attachments to self-esteem during early childhood.
Asunto(s)
Apego a Objetos , Relaciones Padres-Hijo , Grupo Paritario , Autoimagen , Preescolar , Femenino , Humanos , Masculino , Q-Sort , Factores SocioeconómicosRESUMEN
Cell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells. These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy. The intracellular growth of Salmonella enterica occurs in a membranous compartment, the Salmonella-containing vacuole (SCV), and is dependent on effectors translocated to the host cytoplasm by the Salmonella pathogenicity island-2 (SPI-2) encoded type III secretion system (T3SS). Here, we show that bacterial replication is accompanied by the formation of ubiquitinated structures in infected cells. Analysis of bacterial strains carrying mutations in genes encoding SPI-2 T3SS effectors revealed that in epithelial cells, formation of these ubiquitinated structures is dependent on SPI-2 T3SS effector translocation, but is counteracted by the SPI-2 T3SS deubiquitinase SseL. In macrophages, both SPI-2 T3SS-dependent aggregates and aggresome-like induced structures (ALIS) are deubiquitinated by SseL. In the absence of SseL activity, ubiquitinated structures are recognized by the autophagy receptor p62, which recruits LC3 and targets them for autophagic degradation. We found that SseL activity lowers autophagic flux and favours intracellular Salmonella replication. Our data therefore show that there is a host selective autophagy response to intracellular Salmonella infection, which is counteracted by the deubiquitinase SseL.
Asunto(s)
Autofagia , Proteínas Bacterianas/metabolismo , Endopeptidasas/metabolismo , Células Epiteliales/parasitología , Infecciones por Salmonella/metabolismo , Salmonella enterica/enzimología , Animales , Línea Celular , Citosol/metabolismo , Citosol/parasitología , Humanos , Immunoblotting , Inmunoprecipitación , Macrófagos/parasitología , Ratones , Microscopía Confocal , Microscopía Fluorescente , Microscopía Inmunoelectrónica , Ubiquitina/metabolismo , Vacuolas/metabolismo , Vacuolas/parasitologíaRESUMEN
This study examined the stability and growth over a 3-year period of individual differences in preschool children's social competence, which was assessed in three domains: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. A total of 255 children (126 girls and 129 boys) participated in this study. Growth curve analyses demonstrated both stability and change with regard to social competence over early childhood. Social competence measures and latent variables were invariant over this time period, individual differences in social competence were largely stable from year to year, and significant increases over time were observed for the domain most closely reflective of specific personal attributes skills.
Asunto(s)
Conducta Infantil/fisiología , Desarrollo Infantil/fisiología , Individualidad , Habilidades Sociales , Preescolar , Femenino , Humanos , Relaciones Interpersonales , Estudios Longitudinales , Masculino , Grupo Paritario , Factores de TiempoRESUMEN
Autoinducer-2 (AI-2) a signal produced by a range of phylogenetically distant microorganisms, enables inter-species cell-cell communication and regulates many bacterial phenotypes. Certain bacteria can interfere with AI-2-regulated behaviours of neighbouring species by internalizing AI-2 using the Lsr transport system (encoded by the lsr operon). AI-2 imported by the Lsr is phosphorylated by the LsrK kinase and AI-2-phosphate is the inducer of the lsr operon. Here we show that in Escherichia coli the phosphoenolpyruvate phosphotransferase system (PTS) is required for Lsr activation and is essential for AI-2 internalization. Although the phosphorylation state of Enzyme I of PTS is important for this regulation, LsrK is necessary for the phosphorylation of AI-2, indicating that AI-2 is not phosphorylated by PTS. Our results suggest that AI-2 internalization is initiated by a PTS-dependent mechanism, which provides sufficient intracellular AI-2 to relieve repression of the lsr operon and, thus induce depletion of AI-2 from the extracellular environment. The fact that AI-2 internalization is not only controlled by the community-dependent accumulation of AI-2, but also depends on the phosphorylation state of PTS suggests that E. coli can integrate information on the availability of substrates with external communal information to control quorum sensing and its interference.
Asunto(s)
Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimología , Homoserina/análogos & derivados , Lactonas/metabolismo , Sistema de Fosfotransferasa de Azúcar del Fosfoenolpiruvato/metabolismo , Percepción de Quorum , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Homoserina/metabolismo , Mutación , Operón , Sistema de Fosfotransferasa de Azúcar del Fosfoenolpiruvato/genética , Fosforilación , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Activación TranscripcionalRESUMEN
The evolutionary rationale offered by Bowlby implies that secure base relationships are common in child-caregiver dyads and thus, child secure behavior observable across diverse social contexts and cultures. This study offers a test of the universality hypothesis. Trained observers in nine countries used the Attachment Q-set to describe the organization of children's behavior in naturalistic settings. Children (N = 547) were 10-72 months old. Child development experts (N = 81) from all countries provided definitions of optimal child secure base use. Findings indicate that children from all countries use their mother as a secure base. Children's organization of secure base behavior was modestly related to each other both within and across countries. Experts' descriptions of the optimally attached child were highly similar across cultures.
Asunto(s)
Conducta Infantil/fisiología , Desarrollo Infantil/fisiología , Relaciones Madre-Hijo/psicología , Apego a Objetos , Adolescente , Adulto , Actitud del Personal de Salud , Niño , Preescolar , Comparación Transcultural , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Pediatría , Adulto JovenRESUMEN
Children's self-imposed isolation in the company of others (social withdrawal due to shyness or unsociability) and active isolation due to direct aggressive behaviors can challenge successful engagement in the peer group. The developmental attributional perspective acknowledges that children's intended affiliative responses are, in part, guided by their emotions and beliefs toward peers' social behaviors and may differ depending on children's sex, age group, and social behavior. This study aimed to (1) describe preschoolers' beliefs, emotions, and intended affiliative preferences toward aggressive, shy, and unsociable peers, depending on children's sex and age group, and (2) explore the associations between preschoolers' beliefs, emotions and intended affiliative preferences, depending on children's social behaviors and children's sex or age group. A total of 158 preschoolers aged 3-6 years were interviewed, using the Child Attributions Interview to assess their beliefs, emotions and intended affiliative preferences toward peers. Teachers completed the Social Competence and Behavior Evaluation Scale to assess children's prosocial behaviors, aggressive-anger, and anxious-withdrawal. Preschoolers' perspectives toward shy and unsociable peers were less negative than toward aggressive peers. However, participants in our sample were not fully aware of the different intentionality and social motivations of shy and unsociable peers. Higher levels of perceived social standing, social motivation and sympathy predicted higher affiliative preferences toward shy, unsociable, and aggressive peers. However, the magnitude of the associations between preschoolers' beliefs, emotions and intended affiliative preferences differed, depending on children's sex, age group and prosocial behavior, especially toward aggressive and shy peer behaviors. These findings are in line with the developmental attributional perspective, but highlight the need to account for developmental specificities, sex differences in peer relationships and children's individual differences in social behaviors.