1,723,454 research outputs found

    GNF-9228 protects 832/13 cells from ER stress and cytokine-induced cytotoxicity.

    No full text
    A. 832/13 cells were treated with 500 nM thapsigargin (TG) for 6h in the presence and absence of 10 μM GNF-9228. A representative immunoblot of cleaved caspase-3 is shown. B. Bar graph summary of 4 independent densitometric measurements of cleaved caspase-3 in 832/13 cells exposed to 500 nM TG + 10 μM GNF-9228 or DMSO for 6 hours. C. 832/13 cells were pre-treated with 10 μM GNF-9228 or DMSO for 24 h followed by 24 h incubation with two doses of thapsigargin (TG) or a mixture of IL-1β and γ-IFN. Cell viability was measured by MTS assay. (&p$ p < 0.01, comparing GNF-9228 to DMSO- treated cells).</p

    Structures of compounds GNF-9228, GNF-4088 and GNF-1346 and their effects on possible target genes.

    No full text
    A. Structures of three compounds with human islet cell proliferative activity isolated from our 832/13-VGF-luc screen are shown. GNF-9228 and GNF-4088 have very similar structures, whereas GNF-1346 is distinct. B. RT-PCR measurement of Nkx6.1 levels in 832/13 cells following exposure to 10 μM GNF-1346, 10 μM GNF-9228 or vehicle (DMSO) for 6 hours. Five human islet samples from different donors were treated with 10 μM GNF-9228, 10 μM GNF-1346 or DMSO for 6 hours, followed by measurement of the following mRNAs by RT-PCR: C. NKX6.1; D. VGF; E. MYC. Data in panels B-E are expressed as fold-increase in 832/13 cells or islets treated with GNF-1346 or GNF-9228 relative to DMSO-treated, with n = 6 for 832/13 cells and n = 5 for human islet experiments (** p< 0.0001 comparing GNF-9228 or GNF-1346-treated cells to DMSO-treated cells in panel B).</p

    GNF-9228 and GNF-1346 signal by distinct mechanisms relative to DYRK1A inhibitors.

    No full text
    A. Ins1 cells treated with an NFATc1-GFP adenovirus were treated with a range of doses of the DYRK1A inhibitors GNF-4877 or harmine, GNF-9228, or GNF-1346 or DMSO for 2h. Following treatment, cells were fixed and imaged for GFP nuclear localization. Data is quantified as percent of cells with nuclear localization of GFP for n = 3 experiments. B. Representative images showing subcellular localization of NFATc1 in the presence of 10 μM GNF-4877, harmine, GNF-9228, GNF-1346, or DMSO; C. 832/13 cells were transiently transfected with the Vgf-luc plasmid used to generate 832/13-Vgf-luc cells and treated with 10 μM GNF-9228, 5 μM GNF-4877, or 5 μM forskolin for 24 h followed by measurement of luc-generated luminescence. Data are expressed as fold-change relative to DMSO-treated cells in four independent experiments (# p<0.005).</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    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

    Rat islet cell proliferation induced by GNF-9228 is not affected by overexpression of DYRK1A.

    No full text
    Rat islets were transduced with a virus overexpressing DYRK1A (Ad-DYRK1A) or a control virus (Ad-βGal). Islets were cultured in the presence of DMSO, GNF-9228 or GNF-4877 for 72h and total islet cell EdU incorporation was measured. Data represent 3 independent experiments, with * p = 0.013).</p

    GNF-9228 selectively stimulates human Islet β-cell replication.

    No full text
    Intact human islets were cultured for 72 h in the presence of 10 μM GNF-9228 or DMSO (vehicle control). EdU was added for the last 18 h of culture. Islets were dispersed, stained for EdU incorporation and treated with antibodies against EdU, insulin or glucagon, and immunofluorescent signals were detected and quantified with a Thermo Scientific Cellomics CX5 High Content (HC) cell imaging system. A. Low magnification image showing increase in islet cell EdU incorporation (yellow) in GNF-9228 versus DMSO-treated cells, with cells visualized by DAPI staining (blue). B. High magnification image showing two EdU (orange nuclei), insulin (green cytoplasm) co-positive cells and one EdU (orange nucleus), glucagon (blue cytoplasm) co-positive cell. C. Bar graph summary of data expressed as the fold-increase in EdU positive cells across all islet cells assayed (left), in β-cells (EdU and insulin co-positive cells (center), and α-cells (EdU and glucagon positive cells (right), representing experiments performed on 7 independent human islet aliquots (total cells and β-cells) and 5 human islet samples (α-cells), expressed as mean +/- S.E.M.(* p S1 Table for further details.</p

    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 link
    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

    Full text link
    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
    corecore