1,721,010 research outputs found
Defect of CD2- and CD3-mediated activation pathways in T cells of atopic patients: Role of interleukin 2
No full textFK506 binding protein (FKBP) 51 controls "TNF-related apoptosis inducing ligand" (TRAIL) response in melanoma
No full textFKBP51 is a cochaperone that regulates several biological processes in the cell, through protein-protein interaction. Very recently, we have found that FKBP51 is hyperexpressed in malignant melanoma and plays a crucial role in its chemo- and radio-resistance. Downmodulation of FKBP51, by gene silencing, produces an increase of melanoma apoptosis induced by several cytotoxic stimuli. To investigate the mechanism of the increased apoptosis sensitivity of FKBP51-silenced melanoma, we performed a study of protein expression profiles in melanoma cells that were depleted or not of FKBP51, using ionizing radiation (IR) as apoptotic stimulus. Among the multiple signaling pathways that were found modulated in FKBP51-silenced cells, a marked upregulation of TRAIL receptors was found. In particular, the death receptors were significantly increased in FKBP51-depleted cells, while the decoy receptors, that do not transduce death signal, were decreased in the same cells. Among TRAIL receptors, TRAIL R2 (DR5) transduces most efficiently the death signal. Aim of the present study was to validate the increase of DR5 at mRNA and protein level in FKBP51-silenced melanoma cells and investigate the effect of FKBP51 silencing on TRAIL-induced apoptosis. Summary of key findings FKBP51-silencing increased DR5 transcript by 6,1 folds (range 2,8/14,7 folds), in melanoma cells, measured by Real-time PCR. Flow cytometry confirmed the increased expression of DR5 (by more than 100%) in FKBP51 silenced cells, compared with non silenced melanoma cells. The study of apoptosis was in accordance with the expression of death receptors. Indeed, FKBP51 silencing increased TRAIL-induced apoptosis, as suggested by both propidium iodide incorporation and annexin V staining of melanoma cells. Low levels of apoptosis were measured in melanoma cells stimulated with 100ng/ml TRAIL (18 + 6%). By contrast, 39 + 14% of apoptosis was measured in FKBP51-depleted melanoma cells, following TRAIL stimulation (P= 0.01). FKBP51 regulated the acetylation pattern of melanoma as suggested by the reduced amount af acetylated protein in FKBP51 silenced-melanoma cells (D), most interestingly, reduced levels of acetylated Yin Yang 1 transcription factor (YY1) involved in control of DR5 tanscription, were found in FKBP51-silenced melanoma, as suggested by western blot assay. Conclusions FKBP51 gene silencing produces a marked increase in TRAIL sensitivity of melanoma, due to upregulation of TRAIL death receptors. FKBP51 decreases the acetylation pattern of melanoma, and in particular of the DR5 transcriptional repressor YY1, suggesting that epigenetic modification of DNA could be responsible for reduced TRAIL-receptor transcription and resistance to apoptosis of melanoma
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
Alternative splicing of the FKBP5 gene drives alternative macrophage polarization
No full textTumor-associated macrophages (TAMs) affect tumor biology and immune escape. TAMs are in constant transition between M1 (anti-tumor) and M2 (pro-tumor) phenotypes because of high plasticity, which requires a fast change of translational activity. FKBP51 is an immunophilin encoded by the FKBP5 gene that supports NF-κB and STAT1 transcriptional activities, essential features of M1 macrophages. FKBP5 alternative splicing occurs on M2 polarization. The splicing protein is unable to support NF-κB and STAT1 activation, but it upregulates PD-L1 expression
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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