1,720,994 research outputs found
P2X7 Receptor: Warburg effect revisited
No full textAbility to adapt to conditions of limited nutrient supply is a key feature of all cells. This may require a complex re-organization of metabolic pathways to balance energy generation and production of biosynthetic intermediates. Several fast-growing cells overexpress the P2X7 receptor (P2X7R) for extracellular ATP. A peculiar feature of this receptor is that it allows growth in the absence of serum. We show here that transfection of P2X7R allows proliferation of HEK293 (HEK293-P2X7) cells not only in the absence of serum but also in low (4 mM) glucose and strongly increases lactate output compared to mock-transfected cells (HEK293-mock). In HEK293-P2X7 lactate output is further stimulated upon addition of exogenous ATP or of the mitochondrial uncoupler FCCP. In another tumour cell line constitutively expressing the P2X7R, the human neuroblastoma cell line ACN, lactate output is also dependent on P2X7R function. P2X7R-expressing cells up-regulate a) the glucose transporter Glut-1, b) the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), c) pyruvate kinase M2 (PK-M2) and d) pyruvate dehydrogenase kinase 1 (PDHK1), e) increase phosphorylated Akt/PKB (ph- Akt/PKB) and f) the level of intracellular glycogen stores. In HEK293-P2X7 cells glucose deprivation strongly increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level. These data show that the P2X7R has an intrinsic ability to reprogram cell metabolism to meet the needs imposed by adverse environmental conditions
Expression of the P2X7 receptor add metabolic adaptation in serum and glucose deprivation
No full textExpression of the P2X7 receptor and metabolic adaptation in serum and glucose deprivation
No full textOne of the main features in cancers is the adaptation to stressing conditions. This adaptation confers them the ability to
grow under reduced nutrient availability shape. Several findings point to the PI3K/Akt pathway as the main pathway
involved. Lately, adaptation to glucose deprivation, as well as to serum starvation, is considered a crucial event in tumour
progression. Recently, in our laboratory, we have demonstrated a close relationship between expression of the P2X7
receptor and increased proliferation in the absence of serum (Adinolfi et al. 2009). Here, we analyze the adaptation of
HEK293 cells stably expressing the P2X7 receptor (HEK293-P2X7) to two key metabolic stress factors: glucose
deprivation and serum starvation. In the absence of glucose (4 mM), HEK293-P2X7 have a higher growth rate compared
with HEK293 cells transfected with the empty vector (HEK293-mock). In addition, HEK293-P2X7 are shown to produce
twofold more ATP and release twice as much lactate (p<0.05) than HEK293-mock. Moreover, in the absence of serum,
PKM2 and PDHK1 are overexpressed in HEK293-P2X7 and are hypermodulated by the glucose deprivation. GLUT1 is
overexpressed in HEK293-P2X7. Akt is activated in HEK293-P2X7. These observations suggest a higher efficiency in
glucose uptake and employment by HEK293-P2X7, explaining a possible role for the P2X7 receptor in cancer cell survival
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
P2X7 Receptor Function in Bone-Related Cancer
Full text linkModulation of tumor microenvironment by different mediators is central in determining neoplastic formation and progression. Among these molecules extracellular ATP is emerging as a good candidate in promoting cell growth, neovascularization, tumor-host interactions, and metastatization. This paper summarizes recent findings on expression and function of P2X7 receptor for extracellular ATP in primary and metastatic bone cancers. Search of mRNA expression microchip databases and literature analysis demonstrate a high expression of P2X7 in primary bone tumors as well as in other malignancies such as multiple myeloma, neuroblastoma, breast, and prostate cancer. Evidence that P2X7 triggers NFATc1, PI3K/Akt, ROCK, and VEGF pathways in osteoblasts promoting either primary tumor development or osteoblastic lesions is also reported. Moreover, P2X7 receptor is involved in osteoclast differentiation, RANKL expression, matrix metalloproteases and cathepsin secretion thus promoting bone resorption and osteolytic lesions. Taken together these data point to a pivotal role for the P2X7 receptor in bone cancer biology
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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