1,721,011 research outputs found

    Wnt/ -Catenin and MAPK Signaling: Allies and Enemies in Different Battlefields

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    Two papers published in Science Signaling reveal extensive crosstalk between Wnt/-catenin and mitogen-activated protein kinase (MAPK) signaling in cancer. Although both studies describe previously unknown links between these two signaling pathways, the relationship between Wnt/-catenin and MAPK signaling depends on the specific cellular context. Indeed, in melanoma, hyperactivated MAPK signaling down-regulates the Wnt/-catenin signal transduction cascade, thereby establishing a negative crosstalk between the two signaling pathways. In contrast, in colorectal cancer, stimulation of the Wnt/-catenin pathway leads to activation of the MAPK pathway through Ras stabilization, representing an example of positive crosstalk. Moreover, activation of Wnt/-catenin signaling has context-dependent functions that trigger opposing effects on tumor growth. In melanoma, aberrant activation of Wnt/-catenin signaling may have anti- oncogenic functions by promoting programmed cell death; by contrast, in the intestine, Wnt/-catenin signaling drives malignant transformation. Thus, there is no single correct way to target the Wnt/-catenin pathway for all cancers

    Overexpression of the nerve growth factor-inducible PC3 immediate early gene is associated with growth inhibition

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    PC3 (pheochromocytoma cell-3) is an immediate early gene isolated as sequence induced in the rat PC12 cell line during neuronal differentiation by nerve growth factor (NGF). PC3, which is expressed in vivo in the neuroblast when it ceases proliferating and differentiates into a neuron, has partial homology with two antiproliferative genes, BTG1 and Tob. Here we report that overexpression of PC3 in NIH3T3 and PC12 cells leads to marked inhibition of cell proliferation. In stable NIH3T3 clones expressing PC3, the transition from G1 to S phase was impaired, whereas the retinoblastoma (RB) protein was detected as multiple isoforms of M(r) 105,000-115,000 (indicative of a hyperphosphorylated state) only in low-density cultures. Such findings are consistent with a condition of growth inhibition. Thus, PC3 might be a negative regulator of cell proliferation, possibly acting as a transducer of factors influencing cell growth and/or differentiation, such as NGF, by a RB-dependent pathway. This is the first evidence of a NGF-inducible immediate early gene displaying antiproliferative activity

    Arrest of G1-S Progression by the p53-Inducible Gene PC3 Is Rb Dependent and Relies on the Inhibition of Cyclin D1 Transcription

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    The p53-inducible gene PC3 (TIS21, BTG2) is endowed with antiproliferative activity. Here we report that expression of PC3 in cycling cells induced accumulation of hypophosphorylated, growth-inhibitory forms of pRb and led to G1 arrest. This latter was not observed in cells with genetic disruption of the Rb gene, indicating that the PC3-mediated G1 arrest was Rb dependent. Furthermore, (i) the arrest of G1-S transition exerted by PC3 was completely rescued by coexpression of cyclin D1 but not by that of cyclin A or E; (ii) expression of PC3 caused a significant down-regulation of cyclin D1 protein levels, also in Rb-defective cells, accompanied by inhibition of CDK4 activity in vivo; and (iii) the removal from the PC3 molecule of residues 50 to 68, a conserved domain of the PC3/BTG/Tob gene family, which we term GR, led to a loss of the inhibition of proliferation as well as of the down-regulation of cyclin D1 levels. These data point to cyclin D1 down- regulation as the main factor responsible for the growth inhibition by PC3. Such an effect was associated with a decrease of cyclin D1 transcript and of cyclin D1 promoter activity, whereas no effect of PC3 was observed on cyclin D1 protein stability. Taken together, these findings indicate that PC3 impairs G1-S transition by inhibiting pRb function in consequence of a reduction of cyclin D1 levels and that PC3 acts, either directly or indirectly, as a transcriptional regulator of cyclin D1

    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

    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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