1,720,979 research outputs found
New mechanisms involved in the pathogenesis of osteosarcoma
Get PDFOsteosarcoma is the most common and most often fatal primary bone tumour, especially affecting children and adolescents. It is a highly aggressive tumor that develops mainly in the long bones and metastasizes primarily to the lung. Osteosarcoma cells are known to establish a crosstalk with resident bone cells leading to a deleterious vicious cycle.
In this context, we hypothesized that osteosarcoma cells can release in the bone microenvironment transforming extracellular vesicles (EVs) involved in regulating the bone cell proliferation and differentiation, thereby promoting the tumour growth. EVs are small, intact and heterogeneous membrane vesicles that exchange nucleic acids and proteins between cells, inducing phenotypic, biochemical and genetic changes in target cells.
Aim of this thesis is to investigate the role of extracellular vesicles as mediators between cancer cells and resident bone cells.
We used human osteosarcoma cell lines to set protocols aimed at isolating, visualizing and characterizing EVs. Our results showed that osteosarcoma cell lines produce EVs that are able to induce tumour phenotype in recipient murine fibroblasts NIH3T3, as already described for other cancer cell-derived EVs [1,2]. Indeed, in so treated NIH3T3, we observed an enhanced survival capability under low-serum conditions, high levels of activated survival pathways, an increased migration, the acquired capability to grow in an anchorage-independent manner and a de novo expression of osteoblastic and tumorigenic markers. As regarding bone cells, we used as target cells human osteoblasts, their precursors, mesenchymal stromal cells, and human monocytes as osteoclast precursors. The treatment with osteosarcoma-derived EVs induced an increase of MSC differentiation into mature ALP+ and Alizarin red+ cells. EVs derived from osteosarcoma cells promote the migration and the anchorage-independent growth in normal osteoblasts suggesting a transformation toward a tumour-like phenotype. Finally in monocytes, treated with osteosarcoma EVs, we observed an increased proliferation and the formation of TRAP+ multinucleated osteoclasts, because of presence in EVs of cytokines involved in osteoclast activation and differentiation.
These findings highlight the key role of EVs in the crosstalk between the osteosarcoma and bone microenvironment cells, suggesting that further investigation are needed to better define this new field of research.
[1] Antonyak MA, et al. Proc Natl Acad Sci U S A. (2011)4852-7
[2] Li B, et al. Oncogene. (2012) 4740-
The measurement of global shortening as a new parameter to evaluate bone specimen response to uniaxial loading
No full textMechanical load is nowadays considered one of the factor mainly affecting bone tissue properties, both as architecture and functionality. Mechanotransduction is the capability of cells to translate mechanical stresses into biochemical signals, and several studies performed on mouse models demonstrated that also bone cells show a high responsiveness to mechanical stimuli. To date, bone cells mechanotransduction is mainly investigated in animal models, by the use of organ cultures or directly in vivo, and the actual strains induced by the external loads are measured through the use of micro strain gauges placed on the tibia mid-diaphysis. With the aim of proposing a new parameter to come along with the measurement of the actual strains, we exploited the capability of tibial global shortening to return useful information. We employed an experimental system based on a dual mode actuator/transducer with an adequate force range and a high length resolution to retrieve the small shortening of the bone specimens subjected to uniaxially load. Preliminary results showed that the tibia global shortening has a linear relationship with the increasing load, in the range of force usually used in these studies. In addition, the tibia global shortening showed the capability of gathering the changes occurring in the bone tissue mechanical properties when subjecting the specimens to loading signals of different frequencies. When tested with load signals of a frequency equal or higher than 1 Hz, in fact, the bone specimens showed a more rigid behavior. At 9 N of load, for example, the average value of tibia global shortening measured at 0.1 Hz is, on average, 18 % higher than when measured at all the other tested frequencies
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
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