1,720,993 research outputs found
Natural inhibitors of FAAH: a proposed mechanism for the modulation of their activity
No full textGli endocannabinoidi sono una classe di composti lipidici con funzioni neuro- ed immuno-modulatorie identificati di recente. Sono chiamati “endocannabinoidi” poiché sono in grado di legare ed attivare gli stessi recettori attivati dal Δ9-tetraidrocannabinolo (THC), il principio attivo dell’hashish e della marijuana. Nel corso degli ultimi anni sono stati individuati e caratterizzati diversi enzimi responsabili della biosintesi e della degradazione degli endocannabinoidi e ci si riferisce complessivamente a questi con il termine di “sistema endocannabinoide”.
L’anandamide (AEA), uno degli endocannabinoidi più studiati, viene principalmente inattivata dalla idrolasi delle ammidi degli acidi grassi (fatty acid amide hydrolase, FAAH). Tuttavia, in alcuni tipi di cellule come piastrine e leucociti, un metabolismo ossidativo addizionale è stato descritto per questa classe di composti. L’azione della lipossigenasi (LOX) sulla anandamide genera idroperossianandamidi (HpAEA), le quali sono velocemente ridotte a idrossianandamidi (HAEA). Queste ultime sono state testate sugli enzimi del sistema endocannabinoide e risultano possedere una maggiore affinità per la FAAH rispetto all’anandamide stessa, suggerendo una loro azione come inibitori endogeni.
Tra tutti i derivati ossigenati generati dalla LOX, la 15-HAEA risulta essere il più interessante per la sua capacità di inibire selettivamente la FAAH ma non il suo trasportatore (anandamide membrane transporter, AMT), né l’enzima responsabile della produzione di AEA (NAPE-PLD), nè i recettori cannabici (CBRs).
La metilazione e l’acetilazione sono reazioni biochimiche comuni nell’ambiente cellulare ed in questo lavoro abbiamo studiato l’effetto di tali derivati metilati ed acetilati delle HAEA, ipotizzando un’eventuale via di inattivazione di questi composti naturali. Inoltre, abbiamo caratterizzato gli effetti di questi composti sulle altre proteine del sistema endocannabinoide coinvolte sia nel metabolismo dell’AEA che del 2-arachidonilglicerolo (2-AG), dimostrando che questi derivati possono agire come modulatori del riconoscimento molecolare delle HAEA da parte degli elementi del sistema endocannabinoide.
Diversamente dai potenti inibitori sintetici della FAAH finora sviluppati, il vantaggio di questi composti naturali è che tutte le HAEA hanno un effetto reversibile, rappresentando dei candidati ideali per una modulazione flessibile del sistema endocannabinoide in vivo.Endocannabinoids are novel endogenous lipid mediators with neuro- and immuno-modulatory functions. They are called endocannabinoids because they bind the same receptors activated by Δ9-tetrahydrocannabinol (THC), the active principle of hashish and marijuana. Several enzymes for the biosynthesis and degradation of the endocannabinoids have been discovered and characterized, forming the so called “endocannabinoid system”.
Anandamide (AEA), one of the best studied endocannabinoids, is inactivated by fatty acid amide hydrolase (FAAH). However, in some cells like platelets and polymorphonuclear leukocytes an oxidative pathway has also been described. The main products generated by lipoxygenase (LOX) are hydroperoxyanandamides (HpAEAs), which are quickly reduced to hydroxyanandamides (HAEAs). They have been tested on the enzymes of the endocannabinoid system, suggesting they may act as endogenous FAAH inhibitors.
Of all the LOX-generated oxygenated derivates, 15-HAEA appears to be the most interesting, due to its specific ability to inhibit FAAH but not anandamide membrane transporter (AMT) nor N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE–PLD), neither to bind the cannabinoid receptors (CBRs).
Methylation and acetylation are biochemical reactions common in the cellular environment and we investigated whether methylated and acetylated derivatives of HAEAs might affect the inhibitory properties of these natural compounds. Moreover, we investigated the effects of these compounds on the other proteins of the endocannabinoid system. We show that methylated and acetylated derivatives of HAEAs are remarkable modulators of molecular recognition of HAEAs by the elements of the endocannabinoid system.
The advantage of these natural substances, unlike the most powerful synthetic compounds, is that HAEAs are reversible rather than irreversible inhibitors of FAAH, and they seem to be suitable tools for flexible modulation of the endocannabinoid system in vivo
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
Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system
No full textThe family of endocannabinoids contains several polyunsaturated fatty acid amides such as anandamide (AEA), but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta9-tetrahydrocannabinol (Delta9-THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake, through a putative membrane transporter, followed by intracellular degradation by fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutics of potential value for the treatment of pathologies of the central nervous system, and of peripheral tissues. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors, are the topic of this chapter
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
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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