1,720,973 research outputs found

    Role of the β2-adrenergic Receptor (β2AR) on the astrocyte-microglia interaction in in vivo inflammatory model.

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    Astrócitos são importantes células gliais que desempenham um papel fundamental na manutenção da homeostase do Sistema Nervoso Central. Além disso, astrócitos também participam do processo inflamatório que ocorre em doenças como Parkinson, acidente vascular cerebral e Esclerose Múltipla (EM). Nosso grupo está interessado em entender se e como a sinalização pelo receptor β2-adrenérgico (β2AR) pode interferir na função dos astrócitos diante de estímulos inflamatórios. Neste trabalho, apresentamos dados que demonstram que a ativação do β2AR em uma cultura enriquecida de astrócitos regula negativamente a produção induzida por LPS de CCL2 e TNF--α de maneira independente de PKA. Além disso, demonstramos que astrócitos purificados regulam positivamente a expressão de Ccl2, Tnf--α, NOS2 e Il-10 quando tratados com meio condicionado de microglias estimuladas por LPS (MCM, usado como estímulo), em contraste com o controle (não tratado) MCM. E que o pré-tratamento com Fenoterol (agonista β2AR) é capaz de induzir uma regulação positiva de Il-10 e uma regulação negativa da expressão de Ccl2, Tnf--α e NOS2 em astrócitos. Ademais, a ativação de β2AR em astrócitos ou na micróglia estimulada por LPS reduziu os níveis de CCL2 detectados por ELISA no sobrenadante de astrócitos estimulados com o MCM. Também descrevemos que a sinalização pelo β2AR reduz a produção de TNF--α por culturas de microglia estimuladas por LPS. Descrevemos também que o uso de um anticorpo bloqueador anti-TNF--α em estímulos de MCM reverte parcialmente o efeito de LPS-MCM na secreção de CCL2 por astrócitos purificados. Demonstramos que o uso do antagonista β2AR e H89 reverte total e parcialmente, respectivamente, a fosforilação de CREB induzida pelo Fenoterol. Em conclusão, nossos resultados indicam que a interação micróglia-astrócitos desempenha importante papel no microambiente inflamatório, especialmente na secreção de TNF--α pela micróglia, que induz a expressão de importantes citocinas e quimiocinas nos astrócitos. Além disso, nossos resultados demonstram que a sinalização por β2AR regula negativamente o efeito pró-inflamatório da microglia nos astrócitos e na microglia diretamente.Astrocytes are important glial cells that play a key role in maintaining CNS homeostasis. In addition, astrocytes also participate in the inflammatory process that occurs in diseases such as Parkinson\'s, stroke and Multiple Sclerosis (MS). Our group is interested in understanding whether and how β2-adrenergic receptor (β2AR) signaling can interfere with astrocyte function in during inflammatory stimuli. In this work, we present data demonstrating that activation of β2AR in an enriched culture of astrocytes downregulates the LPS-induced production of CCL2 and TNF-α in a PKA-independent manner. Furthermore, we demonstrated that purified astrocytes upregulate the expression of Ccl2, Tnf-a, NOS2 and Il-10 when treated with LPS-stimulated microglia conditioned medium (MCM, used as stimulus), in contrast to the control (untreated) MCM And that pretreatment with Fenoterol (β2AR agonist) is capable of inducing an up-regulation of Il-10 and a down-regulation of the expression of Ccl2, Tnf-a and NOS2 in astrocytes. Furthermore, activation of β2AR in astrocytes or in microglia stimulated by LPS reduced the levels of CCL2 detected by ELISA in the supernatant of astrocytes stimulated with MCM. We also describe that β2AR signaling reduces TNF--α production by LPS-stimulated microglia cultures. We also describe that the use of a blocking anti-TNF--α antibody in MCM stimuli partially reverses the effect of LPS-MCM on the secretion of purified astrocytes of CCL2 and TNF--α. We demonstrated that the use of β2AR and H89 antagonists totally and partially reversed, respectively, Fenoterol-induced CREB phosphorylation. In conclusion, our results indicate that the microglia-astrocyte interaction plays an important role in the inflammatory microenvironment, especially in the secretion of TNF--α by the microglia, which induces the expression of important cytokines and chemokines in astrocytes. Furthermore, our results demonstrate that the β2AR trigger down-regulates the pro-inflammatory effect of microglia on astrocytes and microglia directly

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Neural correlates of food allergy: role of IgE-dependent mechanisms and sensory C-fibers

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    Embora alguns estudos tenham considerado a possibilidade da existência de uma relação direta entre alergia alimentar e alterações de comportamento, são escassas as evidências que sustentem esta hipótese. Relatamos neste trabalho que, após desafio oral com o antígeno, camundongos sensibilizados com ovalbumina (OVA) apresentaram maiores níveis de ansiedade, maiores níveis séricos de corticosterona e aumento da imunorreatividade para Fos no núcleo paraventricular do hipotálamo (PVN) e no núcleo central da amígdala (CeA), áreas cerebrais relacionadas com emotividade. Os neurônios ativados pela alergia alimentar no PVN e no CeA são capazes de produzir fator liberador de corticotrofina (CRF). Os dados também demonstraram que a alergia alimentar leva à ativação do núcleo do trato solitário (NTS). Além disso, observamos que animais imunizados com OVA desenvolveram aversão à ingestão de uma solução contendo clara de ovo. Um tratamento com anticorpo anti-IgE ou a indução de tolerância oral bloquearam tanto o desenvolvimento da aversão à dieta contendo o antígeno quanto a expressão de c-fos no sistema nervoso central (SNC). Para investigar o modo pelo qual se dá a comunicação entre o cérebro e o intestino de animais com alergia alimentar, tratamos camundongos neonatalmente com capsaicina visando a destruição de fibras sensoriais do tipo C. O tratamento com capsaicina, embora não tenha impedido o desenvolvimento da aversão, diminuiu a sua magnitude. Ademais, este tratamento bloqueou completamente a ativação do PVN e diminuiu a expressão de c-fos induzida pela alergia alimentar no núcleo do trato solitário (NTS). Contudo, o tratamento com capsaicina não modificou a imunorreatividade para Fos no CeA de animais imunizados desafiados por via oral com o antígeno. Estes resultados demonstram claramente que a alergia alimentar influencia a atividade do SNC e o comportamento animal. Além disso, os dados obtidos evidenciam a participação de mecanismos dependentes de IgE e das fibras do tipo C na comunicação entre cérebro e o intestino de animais com alergia alimentar. De modo geral, além de enfatizar a relevância da integração entre os sistemas imune e nervoso na elaboração de respostas adaptativas, este estudo fornece subsídios para uma melhor compreensão de possíveis desordens de natureza psicológica em pacientes alérgicos.Although many authors have considered the possibility of a direct interaction between food allergy and behavioral changes, the evidence supporting this hypothesis is elusive. Here we show that after oral OVA challenge allergic mice present higher levels of anxiety, increased serum corticosterone, and increased Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA), which are both emotionality-related brain areas. Food allergy-activated neurons in the PVN and in the CeA are able to produce CRF. We found that food allergy also induced enhanced Fos immunoreactivity in the nucleus of tractus solitarii (NTS) of OVA-immunized animals. Besides that, OVA-immunized animals developed aversion to an antigen-containing solution. Treatment with anti-IgE antibody, or induction of oral tolerance abrogated both food aversion and the expression of c-fos in the central nervous system. In order to investigate the brain-gut communication in allergic animals, we have employed destruction of sensory C fibers by neonatal capsaicin treatment. Although this treatment did not block development of food aversion, it decreased the magnitude of such aversion. Moreover, we observed that while the degree of Fos staining in the NTS of allergic mice was only diminished by neonatal capsaicin, it was completely blocked in the PVN. However, capsaicin did not modify food alergy-induced c-fos expression in the CeA. Besides establishing a direct relationship between brain function and food allergy, our findings provide evidence showing that IgE-dependent mechanisms and the sensory C fibers play an important role in food allergy signaling to the mouse brain. Finally, this study creates a solid ground for understanding the etiology of psychological disorders in allergic patients

    Neural correlates of food allergy: role of IgE-dependent mechanisms and sensory C-fibers

    No full text
    Embora alguns estudos tenham considerado a possibilidade da existência de uma relação direta entre alergia alimentar e alterações de comportamento, são escassas as evidências que sustentem esta hipótese. Relatamos neste trabalho que, após desafio oral com o antígeno, camundongos sensibilizados com ovalbumina (OVA) apresentaram maiores níveis de ansiedade, maiores níveis séricos de corticosterona e aumento da imunorreatividade para Fos no núcleo paraventricular do hipotálamo (PVN) e no núcleo central da amígdala (CeA), áreas cerebrais relacionadas com emotividade. Os neurônios ativados pela alergia alimentar no PVN e no CeA são capazes de produzir fator liberador de corticotrofina (CRF). Os dados também demonstraram que a alergia alimentar leva à ativação do núcleo do trato solitário (NTS). Além disso, observamos que animais imunizados com OVA desenvolveram aversão à ingestão de uma solução contendo clara de ovo. Um tratamento com anticorpo anti-IgE ou a indução de tolerância oral bloquearam tanto o desenvolvimento da aversão à dieta contendo o antígeno quanto a expressão de c-fos no sistema nervoso central (SNC). Para investigar o modo pelo qual se dá a comunicação entre o cérebro e o intestino de animais com alergia alimentar, tratamos camundongos neonatalmente com capsaicina visando a destruição de fibras sensoriais do tipo C. O tratamento com capsaicina, embora não tenha impedido o desenvolvimento da aversão, diminuiu a sua magnitude. Ademais, este tratamento bloqueou completamente a ativação do PVN e diminuiu a expressão de c-fos induzida pela alergia alimentar no núcleo do trato solitário (NTS). Contudo, o tratamento com capsaicina não modificou a imunorreatividade para Fos no CeA de animais imunizados desafiados por via oral com o antígeno. Estes resultados demonstram claramente que a alergia alimentar influencia a atividade do SNC e o comportamento animal. Além disso, os dados obtidos evidenciam a participação de mecanismos dependentes de IgE e das fibras do tipo C na comunicação entre cérebro e o intestino de animais com alergia alimentar. De modo geral, além de enfatizar a relevância da integração entre os sistemas imune e nervoso na elaboração de respostas adaptativas, este estudo fornece subsídios para uma melhor compreensão de possíveis desordens de natureza psicológica em pacientes alérgicos.Although many authors have considered the possibility of a direct interaction between food allergy and behavioral changes, the evidence supporting this hypothesis is elusive. Here we show that after oral OVA challenge allergic mice present higher levels of anxiety, increased serum corticosterone, and increased Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA), which are both emotionality-related brain areas. Food allergy-activated neurons in the PVN and in the CeA are able to produce CRF. We found that food allergy also induced enhanced Fos immunoreactivity in the nucleus of tractus solitarii (NTS) of OVA-immunized animals. Besides that, OVA-immunized animals developed aversion to an antigen-containing solution. Treatment with anti-IgE antibody, or induction of oral tolerance abrogated both food aversion and the expression of c-fos in the central nervous system. In order to investigate the brain-gut communication in allergic animals, we have employed destruction of sensory C fibers by neonatal capsaicin treatment. Although this treatment did not block development of food aversion, it decreased the magnitude of such aversion. Moreover, we observed that while the degree of Fos staining in the NTS of allergic mice was only diminished by neonatal capsaicin, it was completely blocked in the PVN. However, capsaicin did not modify food alergy-induced c-fos expression in the CeA. Besides establishing a direct relationship between brain function and food allergy, our findings provide evidence showing that IgE-dependent mechanisms and the sensory C fibers play an important role in food allergy signaling to the mouse brain. Finally, this study creates a solid ground for understanding the etiology of psychological disorders in allergic patients

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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