74 research outputs found

    Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages

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    <p>Abstract</p> <p>Background</p> <p>Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory <it>cis</it>-elements (motifs) offers a robust approach.</p> <p>Results</p> <p>Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in <it>Mafb</it> deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a <it>C1qa</it> promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the <it>C1qa</it> promoter with the GATA-1 motifs and MafB motifs.</p> <p>Conclusions</p> <p>These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of <it>C1qa</it>. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation.</p

    IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

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    In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects

    Management of Natural History collections: criteria and parameters of evaluation

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    [ES] Las colecciones de historia natural son una herramienta básica para la investigación científica y el estudio de la distribución en el pasado de muchas especies, así como de la propia historia de la ciencia. Además del uso científico de estas colecciones, destacan otros como el histórico, el divulgativo-pedagógico y el estético. De ahí la importancia que tiene una gestión eficaz de las mismas, la cual implica diversos aspectos, que van desde la conservación y su mantenimiento, su inventario, ordenación y procesamiento informático hasta las múltiples tareas relacionadas con su uso en consultas, visitas, préstamos científicos y participación en actividades de carácter divulgativo. En este artículo se examinan los criterios para evaluar la gestión de las colecciones de historia natural y se definen una serie de parámetros, útiles para medir el estado de una colección y su evolución en el tiempo, tanto en su crecimiento como en su uso, principalmente. Se ejemplifica todo ello en el grupo de los poliquetos, del que el Museo Nacional de Ciencias Naturales de Madrid (MNCN) cuenta con una estimable colección, y se comparan los resultados, según varios parámetros seleccionados, con los de otras colecciones de poliquetos de diversas instituciones de todo el mundo.[EN] Natural History collections are a basic and essential tool for scientific research, the study of the distribution in the past of many species of animals and plants and the History of Science. As well as the scientific aspect of these collections, stand outs other uses as the historic one, the educational and the aesthetic. All these are reasons that show the importance of an effective management of the Natural History collections as well as the several tasks related to it, as consults, visits, scientific loans and educational activities. In this article various criteria and useful parameters are provided for evaluating the curatorial state of a Natural History collection and its evolution, both in growth and use mainly. Finally, an example based on the Polychaeta, an estimable group in the Invertebrates Collection of the Museo Nacional de Ciencias Naturales of Madrid (MNCN), is provided. The results of several selected parameters are compared with other Polychaeta collections from several institutions around the world.Peer reviewe

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Down's Syndrome and Psoriasis Vulgaris.

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