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Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13.
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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
The regulation of extra-hepatic coagulation factor X production in alveolar and bronchiolar epithelium
Full text linkIdiopathic pulmonary fibrosis (IPF) is a progressive and debilitating condition with poor survival (median five years) and few effective therapeutic options. IPF results from the misdirected deposition of extra-cellular matrix proteins (ECM) by activated myofibroblasts, which results in occlusion of airspaces, organ dysfunction, and eventual respiratory failure. Current hypotheses posit that chronic injury to the pulmonary epithelium leads to the activation of wound healing programs and that these processes, through abnormal crosstalk between mesenchymal and epithelial cells, remain progressively activated rather than being resolved. Two important factors in this process are the abnormal activation of the coagulation cascade and the presence of oxidative stress. The coagulation proteinase FX is produced locally in the lung and plays a role in experimental fibrosis. Preliminary in vitro work suggested a role for oxidative stress, which itself has also been purported to play an aetiological role in IPF. This resulted in the hypothesis that local production of coagulation proteinases by lung epithelium plays a role in the pathogenesis of IPF and is regulated by oxidative stress. In vitro, the cell line A549, primary human alveolar type II cells (ATII), and primary human bronchiolar epithelial cells (HBECs) were shown to produce F10 mRNA and FX protein at baseline. This production was increased in the presence of reactive oxygen species (ROS). Further, NRF2 was demonstrated to play a role in this production, through the use of agonists, ChIP, and siRNA. In vivo, immunohistochemistry and immunocytochemistry showed the localisation of FX, FVII, and tissue factor (TF) to epithelial cells. Treatment of bleomycin-induced fibrosis with the antioxidant NAC, although showing no effect on disease, reduced F10 mRNA levels and showed an effect on markers of epithelial injury. Together, these studies provide strong evidence for local epithelial production of FX and for oxidative stress and NRF2 signalling in this production
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
Genetically modified cell therapy for the reduction of lung injury
Full text linkPulmonary fibrosis is a feature of a number of important lung diseases, the commonest of which is idiopathic pulmonary fibrosis (IPF). IPF is refractory to current treatments and has a poor prognosis, so development of novel therapeutic strategies is paramount. Injury to the alveolar epithelium plays a central role in the pathogenesis of IPF, and represents a logical therapeutic target. Keratinocyte growth factor (KGF) exerts protective effects on the alveolar epithelium and is a potential therapeutic candidate. There is growing interest in combined gene and cell therapy approaches, and in this study the therapeutic potential of macrophages genetically modified to express KGF was explored in the mouse bleomycin model of pulmonary fibrosis. Lentiviral vectors were generated expressing KGF, and used to transduce murine BMDM and the IC-21 murine macrophage cell line. KGF-transduced IC-21 cells were characterised and were shown to induce proliferation in mouse lung epithelial cells in vitro. A luciferase-expressing lentiviral vector was produced, and IC-21 cell were transduced to express luciferase. Luciferase-transduced IC-21 cells were tracked in vivo using bioluminescence imaging after delivery to the lungs of mice, and were retained in the lungs of bleomycin-treated mice, but not saline-treated controls, and localised to injured areas. KGF-transduced IC-21 cells were delivered to mice during both the inflammatory and fibrotic phases of the mouse bleomycin model, and no improvements in outcomes reflecting alveolar-capillary membrane permeability, inflammation, cytotoxicity and fibrosis were demonstrated. The reasons for the lack of therapeutic efficacy of KGF-transduced macrophages were unclear, but delivery of macrophages per se was associated with an increase in inflammatory mediators. In conclusion, exogenously delivered macrophages were shown to localise to sites of lung injury, but KGF-transduced macrophages were not found to have therapeutic efficacy in bleomycin-treated mice. Future work should better characterise the effects of exogenous macrophage delivery in pulmonary fibrosis
DNA methylation in lung fibroblasts and its role in pulmonary fibrosis
Full text linkAltered methylation and subsequent changes in gene expression have been implicated in several fibroses including lung however, the full extent and role of altered DNA methylation in fibrotic lung fibroblasts is unknown. Emerging evidence also suggests gender-specific methylation differences are common in disease and could elucidate why diseases characterised by pulmonary fibrosis including idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) have a sex-biased prevalence. Using a genome-wide array-based approach, this thesis investigates differentially methylated and expressed genes in fibrotic compared to control lung fibroblasts, gender-specific methylation and expression differences and the effects of modulating DNA methylation using a DNA methyltransferase (DNMT) inhibitor, 5-Aza-2’deoxycytidine (5-Aza). Data show primary human IPF and SSc lung fibroblasts have multiple genes with altered DNA methylation and expression compared to control lung fibroblasts. Multiple biological processes were enriched in these genes, many of which are relevant to fibrosis including, transcriptional regulation, extracellular matrix (ECM) organisation, Wnt signalling and apoptosis. Using siRNA knockdown and collagen gel contraction assays, novel genes including Tenascin-XB (TNXB), which encodes the ECM glycoprotein Tenasicn-X (TNX), were identified as having potential functional significance in the pathogenesis of pulmonary fibrosis. Furthermore, multiple genes including TNXB had altered methylation and expression in IPF compared to SSc lung fibroblasts and may distinguish IPF from other diseases associated with pulmonary fibrosis. Multiple genes were identified with gender-specific differences in methylation and expression in lung fibroblasts. Interestingly, multiple genes with altered methylation in IPF males compared to control males were not the same genes with altered methylation in IPF females compared to control females, which may in part explain why IPF predominates in males. The final chapter of my thesis shows 5-Aza treatment alters the methylation and expression of multiple genes in primary human lung fibroblasts. Strong correlation between changes in methylation and changes in expression were identified suggesting DNA methylation can directly regulate the expression of multiple genes in lung fibroblasts
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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