1,721,139 research outputs found
Inhibition of glucagon-signaling and downstream actions by interleukin 1 beta and tumor necrosis factor alpha in cultured primary rat hepatocytes
No full textIn cultured rat hepatocytes, glucagon increased the phosphoenolpyruvate carboxykinase (PCK1) mRNA by increasing cellular cAMP concentrations. The proinflammatory cytokines rhIL1 beta and rhTNF alpha. impaired the increase both in cAMP and PCK1 mRNA. Glucose formation from glycogen stimulated by glucagon was also attenuated by the cytokines, very likely due to the attenuation of the cAMP increase. Treatment of hepatocytes with the phosphodiesterase inhibitor IBMX or the inhibitory G-protein (G(i)) inactivating compound pertussis toxin did not abolish the inhibition of the glucagon-stimulated increase in cAMP by the cytokines indicating that phosphodiesterase and G(i) were not involved. The activation of adenylate cyclase by forskolin enhanced cAMP and PCK1 mRNA. Again, rhIL1 beta and rhTNF alpha attenuated the increase in PCK1 mRNA, however, not that in cAMP. The stimulation of PCK1 mRNA increase with the nonhydrolyzable cAMP analogue CPT-cAMP was inhibited by rhIL1 beta and rhTNF alpha indicating interference independent of changes in cAMP levels. It is concluded that rhIL1 beta and rhTNF alpha inhibited glucagon-stimulated signal transduction at the site of cAMP formation. In addition, glucagon-stimulated PCK1 mRNA was attenuated independent of cAMP formation very likely on the transcriptional and/or post-transcriptional level
Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes
No full textThe participation of phosphatidylinositol 3-kinase (PI3-kinase), protein kinase C, and mitogen-activated protein kinase (MAP-kinase) in the inhibition by interleukin 6 (IL-6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes, IL-6 or insulin inhibited the glucagon-stimulated increase in PCK messenger RNA (mRNA) by about 70%, In the presence of either the PI3-kinase inhibitor, wortmannin, or the protein kinase C inhibitor, GF109203x, the inhibition by IL-6 was only about 40%, although it was abolished with both inhibitors in combination, Wortmannin alone but not GF109203x prevented the inhibition by insulin of glucagon-stimulated PCK gene expression. The MAP-kinase pathway inhibitor, PD98059, did not affect IL-6 or insulin inhibition of PCK mRNA increase. When chlorophenylthio-cyclic 3',5' adenosine monophosphate (CPT-cAMP) was used instead of glucagon, IL-6 or insulin inhibited the increase in PCK mRNA by 75% and 85%, respectively, The inhibition by IL-6 was only about 50% in the presence of either wortmannin or GF109203x alone but was abolished with the combination of both inhibitors. The inhibition by insulin was only about 50% in the presence of GF109203x and was abolished by wortmannin. The inhibitors did not affect the inhibition by IL-6 or insulin of the glucagon-stimulated increase in cAMP. It is concluded that the inhibition by IL-6 of PCK gene expression involved both PI3-kinase and protein kinase C, whereas the inhibition by insulin required only PI3-kinase. The inhibition occurred downstream from cAMP formation. Hence, IL-6 and insulin may share, in part, common signal transduction pathways in the inhibition of PCK gene expression
Glucagon-stimulated but not isoproterenol-stimulated glucose formation inhibition by interleukin-6 in primary cultured rat hepatocytes
No full textDuring prolonged sepsis, impairment of glucose supply by the liver leads to hypoglycemia. Our aim was to investigate whether proinflammatory cytokine interleukin-6, a major mediator of the hepatic acute phase reaction, could contribute to this impairment by inhibiting hepatic glucose production stimulated by glucagon or isoproterenol in rat hepatocytes. Interleukin-6 inhibited the stimulation of glucose formation from glycogen by glucagon but not by isoproterenol in cultured rat hepatocytes. This was confirmed in the perfused rat liver. In cultured hepatocytes, the increase in cyclic adenosine-3',5'-monophosphate formation by glucagon was inhibited by interleukin-6, which was probably due to attenuation of glucagon binding to the glucagon receptor. The increase in cyclic adenosine-3',5'-monophosphate stimulated by isoproterenol was not affected by interleukin-6. However, the cytokine inhibited both expression of the key gluconeogenic control enzyme, phosphoenolpyruvate carboxykinase, stimulated by glucagon and isoproterenol. Thus, while increased glucose demand during the acute-phase reaction might initially be accomplished by catecholamine-mediated stimulation Of glucose formation from glycogen, inhibition of gluconeogenesis by interleukin-6 may contribute to the impairment of glucose homeostasis during the prolonged acute phase reaction
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Three-dimensional tissue culture as an experimental model for the evaluation of angiogenic factors
No full textPurpose and Methods: Angiogenesis is the formation of new vessels from preexisting capillaries. Under physiological conditions angiogenesis is a rare event in the adult except in females during their reproductive period, where controlled angiogenesis occurs in the ovary during maturation of the follicle and formation of the corpus luteum and in the uterus during the endometrial secretory phase. During pregnancy angiogenesis occurs in the placenta and the growing mammary glands. Angiogenesis is essential for fertility and to ensure an adequate blood Supply for the growing embryo. In order to improve angiogenesis it is essential to know the underlying molecular mechanisms. We know by now that angiogenesis is controlled by the concerted interaction of a variety of factors (e.g. growth factors, extracellular matrix proteins, and matrix proteases). Here, we present and metabolically characterize an experimental system that allows investigation of individual factors as well as their concerted interaction on the process of terminal cell differentiation. Conclusion: By means of this three dimensional experimental system the function of the extracellular matrix, as it is understood today, is clearly mimicked. It serves as a cellular lattice on the one hand but also as a reservoir for growth factors that are sequestered and released according to the cellular metabolism
Three-dimensional tissue culture as an experimental model for the evaluation of angiogenic factors
No full textPurpose and Methods: Angiogenesis is the formation of new vessels from preexisting capillaries. Under physiological conditions angiogenesis is a rare event in the adult except in females during their reproductive period, where controlled angiogenesis occurs in the ovary during maturation of the follicle and formation of the corpus luteum and in the uterus during the endometrial secretory phase. During pregnancy angiogenesis occurs in the placenta and the growing mammary glands. Angiogenesis is essential for fertility and to ensure an adequate blood Supply for the growing embryo. In order to improve angiogenesis it is essential to know the underlying molecular mechanisms. We know by now that angiogenesis is controlled by the concerted interaction of a variety of factors (e.g. growth factors, extracellular matrix proteins, and matrix proteases). Here, we present and metabolically characterize an experimental system that allows investigation of individual factors as well as their concerted interaction on the process of terminal cell differentiation. Conclusion: By means of this three dimensional experimental system the function of the extracellular matrix, as it is understood today, is clearly mimicked. It serves as a cellular lattice on the one hand but also as a reservoir for growth factors that are sequestered and released according to the cellular metabolism
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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