1,721,079 research outputs found
The Transcriptional Regulation of the Tissue Inhibitor of Metalloproteinases-1 (Timp-1) Gene in Hepatic Stellate Cells
No full textThis work has shown in vitro that the AP-1 site at the 5'end of the TIMP-1 minimal promoter is crucial for transcriptional activity in the HSC. Furthermore this study has established that the Jun D homodimer is the main positive regulator of AP-1 mediated TIMP-1 gene transcription. The other endogenous AP-1 proteins, Fos B and Fra 2, were shown to function as negative regulators through their formation of inhibitory heterodimers. In contrast, investigations of the IL-6 promoter indicated that it was differentially regulated from TIMP-1, although both promoters are up regulated in the activated HSC and dependent on Jun D for transcription. The IL-6 promoter activity however, was shown to be dependent on the binding of a Jun D containing dimer but not a homodimer and it was suggested that the positive transcriptional effects were mediated via another as yet undetermined site. Work in N1H3T3 fibroblasts confirmed the classical c-Jun/c-Fos regulation of TIMP-1 transcription in the fibroblast line, suggesting the Jun D mediated mechanism of TIMP-1 regulation may be HSC specific.Investigations in vivo also confirmed the results of the in vitro studies, indicating that HSC activation was accompanied by an increase in Jun D expression and a change in its molecular weight. The change in Jun D size may further regulate gene expression, as the short form of Jun D is believed to be inactive, possessing no transactivation domain.Through the use of a mouse model it was possible to demonstrate that Jun D-/- knockout mice developed significantly less fibrosis than the wild type controls following an 8week CCI4 liver injury. Using Taqman quantitative RT PCR it was possible to demonstrate a biological mechanism for the reduced fibrosis seen in the Jun D-/- knockouts, as their livers contained significantly less TIMP-1 and pro-collagen mRNA than the controls.Other investigations identified that both the SP-1 and LBP-1 sites in the TIMP-1 promoter were crucial for high level transcription. Protein and supershift analysis suggested that the SP-1 binding complexes differ between the HSC and fibroblasts, implicating the interactions of SP-1 & SP-4 and SP-1 & SP-3 respectively. A single strand binding complex was also identified, binding to the first LBP-1 site of the TIMP-1 promoter, however the content and function of this complex is at present unknown.</p
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1
No full textChronic liver injury leads to a progressive wound healing response that eventually results in hepatic fibrosis characterised by net deposition of fibrillar extracellular matrix (ECM) and a qualitative shift from type IV to type I/III collagen. The pivotal cellular event underlying this response is hepatic stellate cell (HSC) activation towards a myofibroblast-like phenotype. Activated HSC contribute to ECM remodelling via secretion of type I/III collagens and matrix metalloproteinases (MMPs). Previous studies showed that three-dimensional (3D) contact of activated HSC with type I collagen further stimulates the ECM remodelling properties of HSC by inducing the type IV gelatinase, MMP-9. The aim of the current study was to confirm transcriptional activation of the MMP-9 gene and identify transcription factors regulating this response. Gelatin zymography and Northern blotting were used to confirm induction of MMP-9 protein and mRNA expression in primary rat HSC cultured in a three-dimensional collagen I gel lattice. MMP-9 promoter studies in transfected HSC and electrophoretic mobility shift assay (EMSA) were employed to study transcriptional events. Both NF-?B and AP-1 DNA were induced in HSC cultured in 3D collagen I gels and binding sites for these factors in the MMP-9 promoter were crucial for induction of transcription. By contrast removal of an Sp1 site in the promoter enhanced transcription, while over-expression of either Sp1 or Sp3 repressed transcription. It is concluded that 3D contact of activated HSC with collagen I stimulates MMP-9 expression by elevating NF-?B and AP-1 activities which are able to overcome the repressive influence of Sp1/Sp3 on MMP-9 gene transcription
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