1,721,002 research outputs found
Ruolo del fattore di trascrizione Snail1 nel processo d'attivazione delle cellule stellate epatiche
Get PDFLiver fibrosis, the final consequence of several types of chronic hepatic injuries, results from chronic damage to the liver in conjunction with the accumulation of fibrillar collagens and ECM proteins, that alters the hepatic architecture. Hepatic stellate cells (HSC) play a pivotal role in the fibrogenic process. These perisinusoidal cells normally contribute to the maintenance of liver homeostasis by secreting growth factors, storing Vitamin A and regulating ECM turnover, and therefore play a key role to maintain the integrity of the space of Disse. Following liver injury, HSC undergo a process of activation, characterized by
morphological and functional changes and acquire a myofibroblast-like phenotype. Activated HSC proliferate and alter ECM composition both qualitatively and quantitatively. The
individuation of factors responsible for HSC transdifferentiation is therefore a fundamental step to understand the physiopathology of hepatic fibrosis.
Snail1 belongs to the Snail gene family of transcription factors, best known for its ability to trigger ephitelial-mesenchymal transition (EMT), converting epithelial cells into mesenchymal cells with migratory properties. Snail genes influence both tissue formation during embryonic development and the acquisition of invasive properties in epithelial tumors.
Snail1 is also a potent survival factor. A number of studies have reported Snail1 overexpression in several pathological conditions associated with the deposition of fibrotic tissue induced by TGF-beta, a potent Snail1 activator and profibrogenic cytokine for HSC. We therefore started examining Snail1 involvement in the hepatic fibrosis process.
To verify if HSC in vitro activation was associated to an increase of Snail1 expression, HSC purified from mice livers have been seeded on uncoated plastic and maintained in culture up to 10 days; mRNA levels of Snail1 and of the activation marker genes alpha-SMA and Col1alpha1 have been assessed by quantitative Real Time RT-PCR. This analysis evidenced that Snail1 expression augments proportionally to the activation state of HSC. Furthermore, we analysed Snail1 localization in HSC by immunocytochemistry, examining cells in culture up to 10 days: we could detect Snail1 nuclear translocation in cells in culture from at least 4 days. Next, we characterized Snail1 expression in vivo using CCl4 treatment as chronic liver injury model. Fibrosis progression has been evaluated by histology and quantitative Real Time RT-PCR
for alpha-SMA and Col1alpha1. Fibrosis development was associated to a significant increase of Snail1 mRNA. Double staining for Snail1 and alpha-SMA in fibrotic livers showed their colocalization in fibrotic septa, suggesting that activated HSC express Snail1 in vivo. Moreover, in in vivo activated HSC Snail1 resulted significantly up-regulated compared to quiescent
HSC, and immunocytochemistry analysis revealed a nuclear localization. Thus, we started functional studies by RNAi and we optimized Snail1 knockdown in primary cultures of HSC
with adenoviral vectors coding shRNA. The data obtained support the role of Snail1 in HSC activation process, since its silencing results in a decrease of mRNA levels of the activation
markers alpha-SMA and Col1alpha1 and of genes involved in the activation process such as ILK and MMP-9. Preliminary data highlight an increase of Snail1 specific transcripts in human fibrotic liver samples compared to healthy controls.
All in all, our data support a role for Snail1 in the development of hepatic fibrosis and evidence its involvement in HSC activation process
CD80 expression is upregulated by TP53 activation in human cancer epithelial cells
Get PDFCD80 is recognized as one of the most potent costimulatory molecules by which immune cells limit cancer progression; however, the current understanding of the regulation of its expression on human tumor cells is limited. The TP53 tumor suppressor plays a critical role in cancer and its significant role in the control of immune responses is emerging. Here, we evaluated the role of TP53 as a regulator of CD80 expression in human cancer cells. A set of well-known TP53–reactivating compounds were used on TP53-wild-type, TP53-deficient, TP53-mutated and TP53-knockdown cancer cell lines to determine if TP53 can regulate CD80. CD80 expression was analyzed in samples from patients with TP53-active vs TP53-inactive Colon Adenocarcinomas (COAD) from TCGA panCancer Atlas. We report that the pharmacological activation of TP53 can stimulate the expression of CD80 in human tumor cells of epithelial origin. We also provide evidence that CD80 expression exhibits a strong correlation with TP53 activation in a subgroup of colon tumors with better overall survival. These results confirm the link between TP53 and immune surveillance in human cancer and provide the possibility that conventional TP53-activation approaches for tumoricidal effects may be repurposed for immunotherapy strategies
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Relationship between virulence factor genes in bovine Staphylococcus aureus subclinical mastitis isolates and binding to anti-adhesin antibodies
No full textStaphylococcus aureus is the most common aetiologic agent of contagious bovine mastitis. It is characterized by a wide array of virulence factors. The differences among strains jeopardize the development of effective vaccines against Staph. aureus mastitis. We tested the immunogenicity of a peptide subunit vaccine coding for three different adhesion factors, fibrinogen-binding protein (Efb), fibronectin-binding protein A (FnbpA) and clumping factor A (ClfA). Then we evaluated the influence of some virulence factors on the ability of specific anti-adhesin antibodies to react with sixteen Staph. aureus strains isolated from bovine subclinical mastitis. Immunization with the recombinant adhesins stimulated a strong humoural (IgG and IgA) and mucosal IgA immune response in all animals tested. Hyperimmune serum recognized with diverse efficiency the sixteen Staph. aureus strains and this circumstance correlated well with the level of expression of adhesins. Among the different virulence factors considered to classify strains, spa gene polymorphisms showed the strongest influence on isolate reactions to hyperimmune serum. Our results indicate the importance of a disease- and environment-specific analysis of isolates. Thus, as opposed to other pathogens to obtain an effective vaccine we should characterize multiple strains and identify the prevalent virulence factors expressed
Repetitive domain of Clostridium difficile toxin B exhibits cytotoxic effects on human intestinal epithelial cells and decreases epithelial barrier function
No full textWe have used recombinant repetitive domain of Clostridium difficile toxin B obtained from two different strains, rec-TcdB3(10463) and rec-TcdB3(8864) and a model intestinal epithelial cell line(s) to characterize their cytotoxic and cytopathic effect and influence on tight-junction organization. Both recombinant receptor binding domains caused intestinal epithelial cell damage, decreased transepithelial electrical resistance and induced translocation of ZO-1 from tight-junction proteins although less efficiently as holotoxins. Recombinant repetitive TcdB domains also caused stimulation of interleukin IL-8 synthesis in HT-29 cells.
This is the first description of glucosyltransferase independent toxicity of TcdB and these C-terminal mediated effects may contribute to the pathophysiology of C difficile infection. (C) 2010 Elsevier Ltd. All rights reserved
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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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