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Effetti degli amminoacidi a catena ramificata (BCAA) sull’eccitabilità di neuroni corticali in coltura primaria e confronto con il modello murino di sclerosi laterale amiotrofica, G93A
Full text linkRecenti studi epidemiologici hanno accertato che, rispetto all’intera popolazione italiana, la categoria dei calciatori presenta una maggiore incidenza di casi di Sclerosi Laterale Amiotrofica (SLA). Una delle principali ipotesi relativa a questo dato è l’eccessivo utilizzo di integratori dietetici e farmaci che servono ad aumentare la performance sportiva ed a diminuire la sensazione di fatica. In particolare, è stato riscontrato che Valina, Leucina e Isoleucina (Branched Chain AminoAcids: BCAA) sono tra i supplementi maggiormente utilizzati tra gli atleti.
Per studiare i possibili effetti dei BCAA sulle proprietà elettriche neuronali sono stati effettuati esperimenti elettrofisiologici sui neuroni corticali primari provenienti da topi di controllo trattati con 200 µM di BCAA, ed i risultati ottenuti sono stati confrontati con quanto osservato nei neuroni di controllo non trattati.
Questi esperimenti hanno dimostrato che il trattamento induce un significativo aumento nell’eccitabilità neuronale in maniera dose e tempo–dipendente, rispetto ai neuroni di controllo non trattati. Inoltre, altri amminoacidi dotati di una catena laterale non ramificata, come per esempio l’Alanina e la Fenilalanina, non causano alcuna alterazione come quella riscontrata in seguito all’esposizione ai BCAA.
Studi condotti in modalità voltage-clamp hanno inoltre dimostrato che i neuroni trattati con i BCAA possiedono correnti voltaggio-dipendenti del Sodio persistente e del Calcio maggiori di quelle dei neuroni di controllo. Ciò indica che le modifiche delle proprietà biofisiche dei potenziali d’azione sono probabilmente dovute all’aumento nella densità in membrana dei canali specifici per queste specie ioniche.
La riscontrata ipereccitabilità e le alterazioni di funzionalità dei canali ionici di Sodio persistente e di Calcio indotte dai BCAA in cellule di controllo sono paragonabili a quelle riscontrate nei neuroni ottenuti da un modello murino di SLA, il topo G93A, evidenziando un’importante correlazione tra le due condizioni sperimentali.
Inoltre, è stato dimostrato che la Rapamicina, farmaco in grado di bloccare il complesso mTOR, favorisce il ripristino di una frequenza di scarica confrontabile con i valori di controllo, sia in cellule trattate con i BCAA che in neuroni G93A. Ciò potrebbe indicare che il complesso mTOR è coinvolto nelle alterazioni indotte dai BCAA e nella patogenesi della SLA.
La comprensione di come i BCAA influiscano sulle proprietà fisiologiche e funzionali dei neuroni corticali può permettere di stabilire un loro possibile coinvolgimento nell’eziopatogenesi della SLA contribuendo alla comprensione del probabile meccanismo d’azione interessato, al fine di individuare nuovi trattamenti terapeutici.Some epidemiological studies have recently ascertained that, Italian soccer players present a higher risk factor for Amyotrophic Lateral Sclerosis (ALS), compared to general population. One of the main hypotheses is related to the abuse of dietary supplements and drugs to enhance sporting performance and to reduce the feeling of fatigue. In particular, it has been reported that Valine, Leucine and Isoleucine (Branched-chain Amino Acids: BCAAs) are widely used among athletes. To study the possible effect of BCAAs on neuronal electrical properties, electrophysiological experiments have been performed on primary cortical neurons treated with 200 µM of BCAA and cultured from control embryos. All data have been compared to control values.
The experiments have demonstrated that the treatment induces a significant increase of neuronal excitability dose- and time-dependent respect to control.
Moreover, the treatment with other aminoacids, such as Alanine and Phenilalanine, doesn’t cause any alteration.
Voltage clamp experiments show that, after a long exposition to BCAA, neurons present an increase of the Sodium and Calcium voltage-dependent channel densities.
So, those biophysical changes could explain the increase of action potential frequencies observed after BCAA exposure.
Both hyperexcitability and the higher Sodium and Calcium densities, induced by BCAA in control cells, were comparable to those obtained in the G93A neurons underlining an important correlation between two experimental conditions.
Moreover, a treatment with Rapamycin, an inhibitor of the complex mTOR, was able to revert both the BCAA-induced and the G93A hyperexcitability to control values.
These findings strongly indicates that in both cases, the mTOR signalling could be activated.
In this way, the understanding of the effect mediated by BCAA on the functionality of primary cortical neurons and the mechanism of action will allow us to learn better the ethiopathogenesis of ALS, thus opening up new strategies for the treatment of this pathology
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
"Voltage-dependent calcium current in cortical neurons are modulated by branched chain amino acids".
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