1,721,061 research outputs found
ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT
Get PDFDefective apoptosis represents one of the major causative factors in the development and progression of cancer. The ability of tumour cells to evade engagement of apoptosis can play a significant role in their resistance to conventional therapeutic regimens. In the last few years, preclinical and clinical studies have indicated ceramide and the enzymes of its metabolism, in particular Acid Sphingomyelinase (A-SMase) which hydrolyzes sphingomyelin to ceramide and phosphocoline, as key players in tumour physiopathology. Different cancers have been shown to have reduced ceramide levels and, of interest, in our previous work we showed that A-SMase down-regulation was a key event in melanoma progression. This event is crucial for the tumours to become more aggressive, but the mechanisms responsible of it haven’t been investigated yet.
Taking into account that there is a complex crosstalk between tumour cells and its immunological microenvironment, in this work we first investigated its possible role in A-SMase downregulation in a melanoma model.
To this purpose we performed in vivo and in vitro experiments which led us to identify tumour associate macrophages (TAM) as possible responsible of A-SMase downregulation through the Ap2-α transcription factor. Moreover, we demonstrated that these molecular changes in tumour cells give, in turn, pro-tumoural and immunosuppressive features to the surrounding microenvironment, with the recruitment of Myeloid-derived suppressor (MDSCs) cells and Regulatory T lymphocytes (TREGS). From these and our previous data, we clearly showed that the ability to create this immunosuppression together with the acquisition of a more aggressive phenotype, both depend on the naturally occurring A-SMase decrease in melanoma cells during tumour progression.
The broad role of A-SMase in tumour pathogenesis we identified, indicates that the enzyme is at the crossroad of key pathways in tumourigenesis. This aspects has clear potential in therapeutic perspective in which A-SMase overexpression or administration might be consider as an useful adjuvant for cancer therapy.
Here we demonstrated for the first time that restoring A-SMase expression in melanoma cells not only reduces tumour growth and immunosuppression, but moreover accounts for a high, unexpected recruitment of immune cells with an anti-tumoural function in the tumour microenvironment, such as Dendritic cells (DCs) and CD4+ and CD8+ T lymphocytes.
In conclusion our results reveal the central role of A-SMase expressed by melanoma cells in orchestrating the cross-talk with the surrounding microenvironment. These interactions are crucial for tumour fate, lying on its rejection or progression. Our observation that A-SMase overexpression “educate” tumour microenvironment against cancer cells, further encourage the use of this enzyme as an adjuvant for cancer therapy
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
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
