1,720,957 research outputs found
Receptor activator of nuclear factor kappa B ligand (RANKL) modulates the expression of genes involved in apoptosis and cell cycle in human osteoclasts
It has been clearly established that receptor activator of nuclear factor kappa B ligand (RANKL) is a key cytokine involved in the differentiation of osteoclastic precursors of the monocytic/macrophagic lineage. However, relatively little information is available on the ability of RANKL to modulate the expression of genes controlling cell survival/apoptosis and proliferation in human osteoclastic cells in comparison to macrophages. For this purpose, CD14+ human peripheral blood mononuclear cells, which express the cognate high affinity receptor activator of nuclear factor kappa B (RANK), were differentiated along the macrophagic or osteoclastic lineage by adding macrophage-colony stimulating factor (M-CSF) or M-CSF plus RANKL in culture for 12 days. RANKL up-regulated the expression of the chemokine MIP1alpha, which potentiates osteoclastic differentiation and simultaneously activated both anti-apoptotic (Bcl-2) and pro-apoptotic (CIDEB, PYCARD, and BAK-1) genes. Moreover, RANKL markedly up-regulated cylin D2, while it significantly decreased the levels of cyclin A, cyclin-dependent kinase 2, and other cyclin-dependent kinases, in keeping with the notion that end-stage osteoclasts are nondividing cells. Finally, a long-term exposure of RANKL up-regulated the adaptor protein TRAF3 but not TRAF6
Recombinant TRAIL induces miorelaxating activity in rat aortas, which is abrogated by the induction of diabetes mellitus
TNF-related apoptosis inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family of cytokines, which exist either as type II membrane or as a soluble protein. Although the best-characterized activity of TRAIL is represented by its anti-cancer activity, it has been recently shown that TRAIL serum levels are decreased in patients affected by atherosclerotic cardiovascular disease raising the possibility that circulating soluble TRAIL might also affect vascular biology. In this respect, it has been previously shown that TRAIL induces the in vitro release of nitric oxide by vascular endothelial cells. In order to explore the in vivo relevance of these in vitro findings, we have assessed the vascular reactivity in response to recombinant TRAIL in a more intact paradigm. For this purpose, rings (4mm long) from rat thoracic aorta were obtained by both control (3-month-old male non-diabetic Wistar rats receiving vehicle infusion) and rats in which diabetes mellitus was induced by injecting 40 mg/kg streptozotocin (SZT). After sacrifice of the animals, aortas were harvested, cleaned of connective tissue and vascular reactivity was analyzed in ex vivo immediately after harvest. During submaximal contraction with phenylephrine, incubation of aortic segments in the presence of increasing (up to 1000 ng/ml) concentrations of recombinant human TRAIL, resulted in significant (p<0.01) vaso-relaxation. The effect was dose-dependent and was completely abolished by pre incubation of the rat aortic rings with L-NAME, clearly indicating that the NOS pathway played a key role in mediating the myo-relaxating activity of TRAIL. In parallel, we have investigated whether the induction of diabetes mellitus might affect the relaxating activity of aortic rings in response to TRAIL. Diabetes mellitus was induced by destruction of pancreatic islet cells by treating rats with SZT (40 mg/kg). Non-fasting blood glucose concentrations of both SZT-diabetic rats (SZT, n = 10) and age-matched control non-diabetic rats treated with vehicle (n = 10) were measured at days 5 and 15, when animals were sacrificed with CO2. The loss of insulin secretion triggered stable hyperglycemia, as evaluated by blood glucose measurement: 260±46 and 295±55 in diabetic rats at days 5 and 15 after diabetic induction, respectively, versus 89±8 in control rats. Relaxation to TRAIL was completely abrogated in aortic rings obtained from SZT-induced diabetic rats. To the best of our knowledge, this is the first demonstration that soluble recombinant TRAIL promotes a dose-dependent myo-relaxation activity when added ex vivo to rat aortic rings, thus suggesting that it might play a physiological role in the control of vascular tone regulation. Importantly, such myorelaxating activity was completely abrogated in diabetic rats, as early as 15 days after diabetes mellitus induction by STZ injection. It should be emphasized that diabetic vascular dysfunction is a major clinical problem that predisposes patients to a variety of cardiovascular diseases. In fact, diabetic patients frequently suffer from macroscopic and microscopic vasculopathy and accelerated atherosclerosis. The loss of myo-relaxating activity is a key feature of endothelial dysfunction, which invariably precedes permanent vascular alterations. Taken together with previous data showing that TRAIL significantly counteracts the pro-adhesive activity of inflammatory cytokines on endothelial cells in vitro and displays anti-atherosclerotic activity when injected in vivo in ApoE−/−null mice, our present findings suggest that a therapeutic strategy aimed to restore the miorelaxating response to TRAIL may be suitable for improving the vascular function in diabetes mellitus
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
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