1,720,979 research outputs found
Clones of aging: When better fitness can be dangerous
Full text linkThe biological and clinical significance of aberrant clonal expansions in aged tissues is being intensely discussed. Evidence is accruing that these clones often result from the normal dynamics of cell turnover in our tissues. The aged tissue microenvironment is prone to favour the emergence of specific clones with higher fitness partly because of an overall decline in cell intrinsic regenerative potential of surrounding counterparts. Thus, expanding clones in aged tissues need not to be mechanistically associated with the development of cancer, albeit this is a possibility. We suggest that growth pattern is a critical phenotypic attribute that impacts on the fate of such clonal proliferations. The acquisition of a better proliferative fitness, coupled with a defect in tissue pattern formation, could represent a dangerous mix setting the stage for their evolution towards neoplasia
Effects of intense physical exercise on osteogenic commitment of mesenchymal progenitors
No full textMultipotent human bone ma rrow stromal cells (hBMSCs) can dif ferentiate into osteoblasts, chondrocyte and adipocytes. MSC commitment toward a s pecif ic cell type is influenced by a multitude of stimuli and inhibitors acting on specif ic transcription factors. RUNX2, SOX9, PPARgamma2 control MSC dif ferentiation toward osteoblast, chondrocyte, adipocyte, respectively. MSCs can also be isola ted from peripheral blood [1]. Circulating MSCs represent an excellent tool for the ex vivo investigation of gene expression patterns in dif ferentiating precur sors. We have investigated how the ex pression levels of ma ster dif ferentiation genes ma y be influenced by intense physical exercise in competitive runners. Eleven ma le subjects were enrolled for collection of peripheral blood samples before and after the Run for Science 42 km ma ra thon. The samples were used to perform i) biochemical, ii) proteomic and iii) molecular analyses in order to evaluate the ef fects of intense physical exercise on bone ma ss and, in particular, on osteogenic commitment of MSC. Comparing pre and post run data we observed a 2fold increase in RUNX2 gene expression and a 2fold decrease in PPA Rga mma2 gene ex pression. Interestingly, we also observed an increased ex pression of S OX9. These preliminary data indicate how intense physica l activity eff ectively favors MSCs osteocondrogen ic commitment at the expense of the mutually exclusive adipogenic commitment. Further investigations at the molecular and biochemical level will clarif y which players trigger the observed cellular response. [1] Valenti MT et al., B one 43 (2008) 10
Runx2 expression: A mesenchymal stem marker for cancer
No full textThe transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically‐expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial‐mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment. However, studies evaluating this gene as a cancer marker are lacking. In the present study, Runx2 expression was analysed in 11 different cancer cell lines not derived from bone tumour. In addition, the presence of Runx2‐related cell‐free RNA was examined in the peripheral blood of 41 patients affected by different forms of tumours. The results demonstrated high expression levels of Runx2 in the cancer cell lines and identified the presence of Runx2‐related cell‐free RNA in the peripheral blood of patients with cancer. As compared with normal individuals, the expression level was increased by 14.2‐fold in patients with bone metastases and by 4.01‐fold in patients without metastases. The results of the present study therefore opens up the possibility to exploit Runx2 expression as a cancer biomarker allowing the use of minimally invasive approaches for diagnosis and follow-up
Cellular response to physical exercise: analysis of serum proteins modulation and expression profiles in circulating progenitor cells
Full text linkPhysical activity plays an important role against pathological degenerative conditions and metabolic diseases. In particular, it works as a modulator of the mutually exclusive osteogenic or adipogenic fates of mesenchymal stem cells through a direct action on differentiation-related gene expression. On the other hand, it has also been reported that oxidative stress generated by strenous physical efforts (e.g. marathon running) can affect cell functions. The purpose of this study was to investigate the effects induced by a half marathon in male amateur runners. In particular the investigation focused on: i) serum proteins modulation in response to the oxidative environment, ii) the modulation of circulating progenitor cells commitment, monitored in terms of gene expression; iii) progenitor cells proliferation and homeostasis, monitored through the expression levels of genes related to telomerase activity and autophagic induction, respectively; iv) the effects of soluble factors present in runners’ sera on differentiation process in an in vitro cellular model. The shotgun proteomic approach applied to runners’ sera confirmed the production of reactive oxygen species, counteracted by an increased production of detoxifying and scavenger proteins. Overall, the proteome modulation profile suggests a consequent positive effect of the trained condition. Gene expression analyses showed an upregulation of osteogenesis related genes in Circulating Progenitor cells (CPs) after training, in particular RUNX2 and BMPs. In addition, chondrogenesis related genes such as SOX9, COMP and COL2A1 were upregulated after the run. At the same time, the higher expression of BMP3 suggests a stimulation of CPs proliferation which justifies as well the increased expression of telomerase-related genes, TERT and TERF1. The enhanced expression of autophagyrelated genes (ATG3 and ULK1) correlates positively with the induction of MSCs differentition. Data based on an in vitro model (i.e. Bone Marrow-derived MSCs supplemented with pre- and post-run sera), suggest that intense physical exercise enhances BM-MSC potential for osteo-chondrogenic commitment at the expense of the mutually exclusive adipogenesis. The in vitro deposition of calcium salts demonstrates mineralization, i.e. complete maturation of osteoblasts promoted by soluble factors in runners’ sera. In conclusion, changes induced by physical activity may be considered positive in terms of: i) oxidative stress management during oxigen reactive species production; ii) progenitor cells proliferation, under autophagy-mediated positive selection; iii) osteochondrogenic induction of CPs; iv) production of circulating soluble factors which support complete maturation of committed osteoblasts. All data seem to suggest that physical activity has positive effects on overall health
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
Effects of oral anticoagulant therapy on gene expression in crosstalk between osteogenic progenitor cells and endothelial cells
Full text linkDirect oral anti-coagulants (DOACs) are employed in clinical practice for the prevention and treatment of recurrent venous thromboembolism and for the prevention of stroke in non-valvular atrial fibrillation. DOACs directly and reversibly inhibit activated factor X or thrombin and can interfere with other pathophysiological processes such as inflammation, lipid metabolism, and bone turnover. We aimed to evaluate the possible effects of DOACs on osteogenesis and angiogenesis. We treated 34 patients affected by cardiovascular disorders with DOACs; biochemical and molecular analyses were performed before and after three months of treatment. Circulating progenitors (CPs; CD34-, CD45-, CD14-, CD73+, CD105+), which share typical bone marrow stem cell (MSCs) features, were harvested from peripheral blood of the study subjects to monitor the expression of osteogenesis-related genes RUNX2 and SPARC. Human umbilical vein endothelial cells (HUVECs) were used to probe angiogenesis-related VEGF, CD31, and CD105 gene expression. We performed co-culture experiments using a commercial human mesenchymal stem cells line (hMSCs) obtained from bone marrow and HUVECs. Clinical parameters related to bone metabolism, coagulation, renal and liver function, and the lipid profile were evaluated. Values of the C-terminal telopeptide type I collagen (CTX) increased after the treatment. We found a significant increase in osteogenesis marker gene expression in CPs after three months of anticoagulant therapy. An increase in the RUNX2 expression determinant alone was detected instead in hMSCs co-cultured with HUVECs in the presence of treated patients' sera. The VEGF, CD31, and CD105 marker genes appeared to be significantly upregulated in HUVECs co-cultured with hMSCs in the presence of treated patients' sera. Under these conditions, new vessel formation increased as well. Our results highlight an unexpected influence of DOAC therapy on osteogenic commitment and vascular endothelial function promotion
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
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