1,720,979 research outputs found
Novel pathways induced by melatonin on leukocytes: possible pharmacological and inflammatory perspectives
Full text linkLa melatonina, oltre ad essere un regolatore dei ritmi circadiani, è stato recentemente dimostrato essere un modulatore del sistema immunitario attraverso il controllo del comportamento dei leucociti, i quali sono infatti in grado di sintetizzare la melatonina e possiedono specifici recettori di membrana (MT1 e MT2) ad alta affinità (1nM). L’abilità della melatonina di contrastare l’apoptosi sta ricevendo un grande interesse, un effetto ben accetto, nonostante il suo meccanismo sia ancora abbastanza controverso. In questo studio analizziamo il meccanismo coinvolto nell’effetto anti-apoptotico della melatonina in leucociti normali e tumorali. Abbiamo visto che questo effetto è dovuto a due differenti meccanismi cooperanti i quali coinvolgono due target primari con cui la melatonina interagisce; i recettori MT1/MT2 e la calmodulina, un noto target della melatonina a bassa affinità (63 uM). L’interazione con il recettore ed il legame alla calmodulina da origine a due pathways di trasduzione del segnale indipendenti, che consisono da una parte in una trasduzione del segnale canonica (convolgendo le proteine G e la fosfolipasi C), e dall’altra nell’attivazione della 5-lipossigenasi (5-LOX) tramite calmodulina /fosfolipasi A2 (un noto interattore della calmodulina) che termina con la produzione dei 5-HETE. Questi due pathways convergono nell’effetto anti-apoptotico di melatonina a livello mitocondriale, prevenendo l’attivazione di Bax, la chiave che innesca il pathway apoptotico intrinseco. La novità di questi risultati è che Bax è mantenuto nel mitocondrio in una stato anti-apoptotico. Infatti, la melatonina causa la translocazione di Bcl-2 al mitocondrio, dove si lega direttamente a Bax, inibendo la sua attivazione/dimerizzazione. L’effetto anti-apoptotico è completamente abrogato se uno o l’altro pathway viene inibito. La necessità del legame a bassa affinità con la calmodulina, spiega la necessità di alte dosi di melatonina (>100uM). Il coinvolgimento della 5-LOX nell’effetto anti-apoptotico della melatonina è particolarmente interessante dal momento che la necessità di un enzima chiave della risposta infiammatoria può fare nuova luce sul ruolo che la melatonina gioca nella regolazione della risposta immunitaria. Inoltre, l’attivazione della LOX implica uno sprigionarsi di radicali liberi che immediatamente (<1min) e fortemente (fino a 15 volte) segue alla somministrazione di melatonina, raggiungendo un picco a 2 ore per tornare a valori di controllo a 6 ore. Questo è un effetto biologico pro-ossidante che co-esiste e contrasta con la nota abilità della melatonina di radical scavanger.Melatonin, in addition to its main role as regulator of circadian rhythms, has recently been shown to modulate immune functions by controlling the behaviour of leukocytes, which are indeed able to synthesize melatonin and possess the specific high affinity (1nM) plasma membrane receptors (MT1 and MT2). Great interest is receiving the ability of melatonin to contrast apoptosis, a well accepted fact whose mechanisms however are still quite controversial. In this study, we analyze the mechanisms involved in the anti-apoptotic effect of melatonin in normal and tumor leukocytes. We have shown that this effect is due to two different, cooperating mechanisms, involving two primary targets melatonin directly interacts with, i.e., MT1/MT2 receptors; and calmodulin, a known melatonin low affinity (63uM) target. Receptor engagement and calmodulin binding give rise to two independent signal transduction pathways, consisting of a canonical MT1/MT2 receptor mediated signal transduction (involving G protein and phospholipase C) on the one side, and calmodulin/phospholipase A2 (a known calmodulin interactor)/5-lipoxygenase (LOX) activation culminating in 5-HETE production, on the other. These pathways converge into melatonin anti-apoptotic effect at the mitochondrial level, preventing the activation of Bax, the key trigger of the intrinsic apoptotic pathway. The novelty of this finding is that Bax is maintained within mitochondria in an anti-apoptotic state. Indeed, melatonin causes the translocation of Bcl-2 to mitochondria, which directly binds to Bax inhibiting its activation/dimerization. The anti-apoptotic effect is completely abrogated if one or the other pathway is inhibited. The necessity of the low affinity calmodulin binding explains the requirement of high melatonin doses (>100uM). The involvement of 5-LOX in the anti-apoptotic effect of melatonin is particularly intriguing since, the recruitment of a key enzyme of the inflammatory response may shed new lights on the role melatonin plays in the regulation of the immune response. Moreover, LOX activation implies a burst of free radicals that immediately (<1min) and strongly (up to 15folds) follows melatonin administration, peaking at 2hrs to go back to normal values at 6hrs. This is a biological pro-oxidant effect that co-exists with, and contrasts, the well known chemical radical scavenging ability of the melatonin molecule
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
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
Neuroprotection by melatonin on astrocytoma cell death
No full textGlial cells play an active role in the homeostatic regulation of the central nervous system (CNS). Astrocytes, the most abundant glial cell types in the brain, provide mechanical and metabolic support for neurons. The regulation of astrocyte apoptosis, therefore, is important for physiological and pathological processes in the CNS. Melatonin is a neurohormone that regulates target cells via binding to specific high-affinity plasma membrane receptors, MT1/MT2. In addition to regulating circadian rhythms, melatonin has recently attracted much interest for its potential regulation of cell apoptosis. We recently showed that melatonin antagonizes apoptosis on U937 cells via intersecting signal transduction events involving binding to MT1/MT2 and activation of lipoxygenase. Here we describe the neuroprotective potential of melatonin, showing that melatonin significantly reduces damage-induced apoptosis in astrocytoma cells. The mechanism of protection is different from that shown in U937 cells, because it does not involve MT1/MT2 or lipoxygenase; likewise, Ca(2+) influx is not involved. Intriguingly, inhibition of phospholipase C (PLC) with neomycin reverses melatonin protection, suggesting that a PLC-dependent signal transduction, different from that triggered by MT1/MT2, is involved in the antiapoptotic pathway of melatonin
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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