Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring

The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate-early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors

Publications about nursing education in the Revista da Escola de Enfermagem da USP

Scientific production in nursing education field provide important contributions to professional formation and nursing practice. Since we believe this perspective, we carried out a survey aimed at identifying and analyzing nursing education-related articles, building empiric categories from the collected data. This revision is a bibliographical, descriptive and quantitative survey using as source articles published in the Revista da Escola de Enfermagem da USP from 1967 to 2002. We have found 1,137 articles, of which 14.2% refer to nursing education, 89.0% of which are concerned with the undergraduate level. The descriptive analysis of nursing education-related bibliography gives rise to issues concerning the development of research that follow changes in the legislation changes and the demands of the professional market.Produções científicas na área de ensino em enfermagem fornecem importantes contribuições para a formação de profissionais e exercício da enfermagem. Acreditando nesta perspectiva, foi realizado um estudo visando a identificar e analisar os artigos publicados na área de ensino em enfermagem, construindo categorias empíricas com base nos dados coletados. Trata-se de uma pesquisa bibliográfica, descritiva e quantitativa, tendo como fonte artigos publicados na Revista da Escola de Enfermagem da USP, durante o período de 1967 a 2002. Foram encontrados 1.137 artigos, sendo que 14,2% destes referem-se ao ensino de enfermagem, dos quais 89,0% dizem respeito à área de graduação. A análise descritiva dos artigos publicados, referentes ao ensino de enfermagem, desperta a preocupação sobre o desenvolvimento de pesquisas relacionadas ao tema e que acompanhem as mudanças das legislações e as exigências do mercado de trabalho.Producciones científicas en el área de la enseñanza en enfermería ofrecen importantes contribuciones para la formación de profesionales y el ejercicio de la enfermería. Creyendo en esta perspectiva, fue realizado un estudio visando identificar y analizar los artículos publicados en el área de la enseñanza en enfermería, construyendo categorías empíricas a partir de los datos recolectados. Se trata de una investigación bibliográfica, descriptiva y cuantitativa, teniendo como fuente artículos publicados en la Revista da Escola de Enfermagem da USP, durante el período de 1967 a 2002. Fueron encontrados 1,137 artículos de los cuales el 14,2% se refieren a la enseñanza de enfermería, y de éstos el 89,0% se refieren al área del pre grado. El análisis descriptivo de los artículos publicados, referentes a la enseñanza de enfermería, despierta preocupación sobre el desarrollo de investigaciones relacionadas al tema y que acompañen los cambios de las legislaciones y las exigencias del mercado de trabajo

Nursing teaching and the national curricular directives: utopia x reality

Este artículo pretende provocar reflexiones acerca de la enseñanza de la enfermería a la luz de las Directivas Curriculares del Pregrado de Enfermería y su relación con las políticas de salud y el actual mercado de trabajo. Los hechos relatados muestran que los cambios curriculares, en la enseñanza de la enfermería en Brasil, estuvieron históricamente centrados en la adecuación de la formación del enfermero a los intereses del mercado de trabajo. Entretanto, el reto en la formación precisa sobrepasar el foco de esos intereses e insertar efectivamente al futuro enfermero en el sistema de salud, comprometido con las transformaciones exigidas por el ejercicio de la ciudadanía.This article aims at provoking reflections concerning Nursing education in the light of the Curricular Directives for the Undergraduate Course in Nursing and their relation to health policies and the current labor market. The facts reported show curricular changes in Nursing education in Brazil have historically been concerned with the adequacy of the nurse's formation to the interests of the labor market. However, the challenge in nurse's formation needs to overcome the focus of these interests and to effectively insert the future nurse into the health system, committed to the transformations demanded for the exercise of citizenship.Este artigo busca provocar reflexões acerca do ensino de enfermagem à luz das Diretrizes Curriculares do Curso de Graduação de Enfermagem e sua relação com as políticas de saúde e o mercado de trabalho atual. Os fatos relatados mostram que as mudanças curriculares, no ensino de enfermagem no Brasil, tiveram historicamente a preocupação com a adequação da formação do enfermeiro aos interesses do mercado de trabalho. Entretanto, o desafio na formação precisa transpor o foco desses interesses e inserir efetivamente o futuro enfermeiro no sistema de saúde, comprometido com as transformações exigidas pelo exercício da cidadania

Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1

Background: AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo. Methods and Findings: The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo. Conclusions: These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood transplantation in adults, in whom stem and progenitor cell numbers are often limiting. © 2007 Tsuzuki et al

Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation

Post-transcriptional gene regulation in T cells is dynamic and complex as targeted transcripts respond to various factors. This is evident for the Icos mRNA encoding an essential costimulatory receptor that is regulated by several RNA-binding proteins (RBP), including Roquin-1 and Roquin-2. Here, we identify a core RBPome of 798 mouse and 801 human T cell proteins by utilizing global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS). The RBPome includes Stat1, Stat4 and Vav1 proteins suggesting unexpected functions for these transcription factors and signal transducers. Based on proximity to Roquin-1, we select \~50 RBPs for testing coregulation of Roquin-1/2 targets by induced expression in wild-type or Roquin-1/2-deficient T cells. Besides Roquin-independent contributions from Rbms1 and Cpeb4 we also show Roquin-1/2-dependent and target-specific coregulation of Icos by Celf1 and Igf2bp3. Connecting the cellular RBPome in a post-transcriptional context, we find contributions from multiple RBPs to the prototypic regulation of mRNA targets by individual trans-acting factors

The effect of surfactant chain length on the morphology of poly(methyl methacrylate) microcapsules for fragrance oil encapsulation

The solvent evaporation method for producing microcapsules relies upon the correct wetting conditions between the three phases involved in the synthesis to allow core-shell morphologies to form. By measuring the interfacial tensions between the oil, polymer and aqueous phases, spreading coefficients can be calculated, allowing the capsule morphology to be predicted. In this work we explore the effect of surfactant chain length on capsule morphology using poly(methyl methacrylate) as the polymer and hexadecane as the core. We compared the predicted morphologies obtained using the polymer as a solid, and the polymer dissolved in dichloromethane to represent the point at which capsule formation begins. We found that using the polymer in its final, solid form gave predictions which were more consistent with our observations. The method was applied to successfully predict the capsule morphologies obtained when commercial fragrance oils were encapsulated

Effect of organic tomato (Lycopersicon esculentum) extract on the genotoxicity of doxorubicin in the Drosophila wing spot test

The consumption of organic tomatoes (ORTs) reduces the risk of harmful effects to humans and the environment caused by exposure to toxic agrochemicals. In this study, we used the somatic mutation and recombination test (SMART) of wing spots in Drosophila melanogaster to evaluate the genotoxicity of ORT and the effect of cotreatment with ORT on the genotoxicity of Doxorubicin® (DXR, a cancer chemotherapeutic agent) that is mediated by free radical formation. Standard (ST) cross larvae were treated chronically with solutions containing 25%, 50% or 100% of an aqueous extract of ORT, in the absence and presence of DXR (0.125 mg/mL), and the number of mutant spots on the wings of emergent flies was counted. ORT alone was not genotoxic but enhanced the toxicity of DXR when administered concomitantly with DXR. The ORT-enhanced frequency of spots induced by DXR may have resulted from the interaction of ORT with the enzymatic systems that catalyze the metabolic detoxification of this drug

Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows

Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice

A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5 on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears