1,720,981 research outputs found

    Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal

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    We have previously shown that cytokine-induced production of interleukin-6 (IL-6) by cultured bone marrow-derived stromal and osteoblastic cells is inhibited by 17 beta-estradiol, and that estrogen withdrawal (ovariectomy) in mice causes an up-regulation of osteoclast development which can be prevented by a neutralizing antibody against IL-6 or estrogen replacement. To directly establish the link between estrogen loss and altered IL-6 production, implied by our earlier studies, we have now compared IL-6 production in ex vivo cultures of bone marrow cells from mice that were sham operated, ovariectomized, or ovariectomized and treated with 17 beta-estradiol. In addition, we have examined the effect of the in vitro withdrawal of estrogens from primary cell cultures of neonatal murine calvaria on IL-6 production. IL-6 production in ex vivo cultures of bone marrow cells maintained in the presence of 1,25-dihydroxyvitamin D3 or PTH was greater in marrow cells from ovariectomized mice than in those from sham-operated animals or ovariectomized animals receiving estrogen replacement. In line with this finding, addition of 17 beta-estradiol to calvaria cell cultures followed by withdrawal of the steroid caused an increase in the amount of IL-6 produced in response to the subsequent stimulation of these cultures with IL-1 or PTH compared to that in cultures that had never been treated with estradiol; when the inactive isomer 17 alpha- estradiol was used, no change in IL-6 production was observed. These results establish that estrogen loss causes an up-regulation of IL-6 production by bone marrow cells and that a similar phenomenon can be elicited in vitro by withdrawal of 17 beta-estradiol from primary cultures of bone cells

    The RANKL distal control region is required for the increase in RANKL expression, but not the bone loss, associated with hyperparathyroidism or lactation in adult mice.

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    Osteoclast-mediated bone resorption plays an essential role in calcium homeostasis and lactation. The cytokine receptor activator of nuclear factor κB ligand (RANKL) is one of a number of factors that controls the production, survival, and activity of osteoclasts. Calciotropic hormones, such as PTH, control RANKL transcription in part via an enhancer known as the distal control region (DCR), and mice lacking this enhancer have fewer osteoclasts under normal physiological conditions. Here, we have addressed the role of the DCR in situations in which activation of the PTH receptor is thought to stimulate bone resorption via elevation of RANKL expression. Dietary calcium deficiency stimulated RANKL expression in the bone of young (1 month old) wild-type, but not DCR knockout (KO), mice. Consistent with this, the cancellous bone loss and the increase in osteoclasts caused by dietary calcium deficiency were blunted in young KO mice. DCR deletion also prevented the increase in RANKL expression caused by dietary calcium deficiency in 6-month-old mice. However, the diet-induced bone loss was similar in wild-type and KO mice at this age. The increase in RANKL expression caused by lactation was also blunted in DCR KO mice, but lactation-induced bone loss was similar in both genotypes. These results demonstrate that, even though the DCR is required for the increase in RANKL expression associated with hyperparathyroidism or lactation, this increase is not required for the bone loss caused by these conditions in adult mice, suggesting that changes in other factors, such as osteoprotegerin or estrogen levels, play a dominant role

    Demonstration of estrogen and vitamin D receptors in bone marrow-derived stromal cells: up-regulation of the estrogen receptor by 1,25-dihydroxyvitamin-D3

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    We have shown earlier that 17 beta-estradiol inhibits cytokine-induced interleukin-6 (IL-6) production by bone marrow-derived stromal cells as well as osteoblasts, two types of cells with a critical influence on osteoclast development, and that ovariectomy causes an IL-6-mediated up-regulation of osteoclastogenesis in mice. Prompted by this, we have searched here for the presence of estrogen receptors (ERs) in two murine bone marrow- derived stromal cell lines, +/+ LDA11 and MBA 13.2, and the osteoblast- like cell line MC3T3-E1. All three cell lines exhibited high affinity saturable binding for [125I]17 beta-estradiol with a dissociation constant of approximately 10(-10) M and concentration of binding sites of 260 +/- 30, 170 +/- 10, and 90 +/- 10 sites per cell, respectively. In addition, we amplified complementary DNA from the stromal cell lines by polymerase chain reaction using oligonucleotide primers flanking the DNA binding domain of the murine uterine ER. The amplified product showed an identical nucleotide sequence to the DNA binding domain of the murine uterine receptor. Consistent with the functionality of the ER in stromal cells, and specifically its role in the regulation of IL-6 by 17 beta-estradiol, we found that the pure estrogen antagonist ICI 164,384 completely prevented the effect of 17 beta-estradiol on IL-6. All three cell lines also expressed receptors for 1,25-dihydroxyvitamin-D3 [1,25(OH)2D3] (dissociation constant, approximately 10(-10) M), with a concentration of binding sites of 490 +/- 20, 920 +/- 20, and 1110 +/- 70 sites per cell, respectively. 1,25(OH)2D3 treatment of the stromal cells caused a 2-fold increase in the http://www.ncbi.nlm.nih.gov/pubmed Pagina 4 di 10passeri G - PubMed - NCBI 19/07/12 14.34 concentration of ERs and a decrease in cell proliferation. These data establish that bone marrow-derived stromal cells express functional estrogen as well as vitamin D receptors, which serve to mediate actions of their respective ligands on the biosynthetic activity of these cells and presumably the effects of these two steroid hormones on osteoclastogenesis

    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

    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
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