1,721,030 research outputs found
Ruolo della proteina PDZ LIN-7 nella generazione e organizzazione del dominio giunzionale
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A cell culture model to investigate the role of microglia in amyotrophic lateral sclerosis (als)
No full textDespite the selectivity of motoneuron damage in amyotrophic lateral sclerosis (ALS), increasing evidence indicates a participation of microglial cells to motoneuron degeneration in human and murine ALS. Microglia are the resident immune−competent cells of the CNS; notious stimulus may elicit microglia activation and release of toxic factors that accelerate neuronal degeneration and death. However, it is unknown how microglia communicates damage to motoneurons.
To unravel the contribution of microglial cells to the pathogenesis of ALS, we are testing the hypothesis of altered pathways of secretion induced by ALS linked mutant superoxide dismutase (mtSOD1) expression in microglia. To this purpose we have recently established cell culture models consisting in human microglial N9 cell lines stably transfected with wild type or G93ASOD1.
Our data indicate that the expression of mutant SOD1 increases the release of potentially toxic molecules including mtSOD1, whereas the expression of even higher amount of wt SOD1 does not change the pattern of secretion in N9 microglial cells. Moreover, we have also data suggesting that mt SOD1 is released via unconventional pathways not involving the endoplasmic reticulum-Golgi complex route. We are now performing experiments aimed at identifying the secretory pathway of mutant SOD1, which is a crucial step in order to develop appropriate therapeutic strategies to prevent microglial toxicity
PKC and calcineurin regulated trafficking of glutamate transporters
No full textGlutamate transporters play a fundamental role in maintaining extracellular glutamate below neurotoxic levels, and decreased glutamate transport activity is involved in neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Amyotrophic lateral sclerosis (ALS). The transport activity and surface expression of neurotransmitter transporters are often dynamically regulated through modulation of their intracellular trafficking. In the Madin-Darby canine kidney (MDCK) cell line, we have shown that PKC activation induces a time-dependent decrease in glutamate transport activity associated with internalization of the transporter and relocation to recycling endosomes within 20 minutes. Using 32P-metabolic labeling experiments, we showed that PKC activation induces an early transitory peak of phosphorylation of a surface transporter otherwise dephosphorylated (5-10 minutes), and that accumulation in recycling compartments coincides with dephosphorylation of EAAC1 to its basal level. In addition, we found that PKC-induced decrease in transport activity and intracellular relocation of surface EAAC1 also depended on the phosphatase activity of calcineurin. In sharp contrast, we found that internalization and relocation of the GLT1 astroglial glutamate transporter to EAAC1 containing recycling compartments was dependent on PKC activation but independent of calcineurin activity. Moreover, analyses of GLT1 and EAAC1 chimeras revealed that the cytosolic tail of EAAC1 (last 91 cytosolic C-terminal residues) containing sequences for regulated trafficking of this transporter (Cheng et al., 2002; Sheldon et al., 2006) was sufficient to confer calcineurin dependence to PKC induced internalization of GLT1. We are currently investigating the possibility that the tail of EAAC1 targets the protein to specific pathways of endocytosis sensitive to calcineurin activity. The existence of different mechanisms to modulate the trafficking of a specific glutamate transporter may explain the exclusive reduction of GLT1 in ALS
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
La gestione del rischio operativo negli intermediari finanziari: l’inclusione delle correlazioni
No full textLa tesi sviluppa l’analisi del rischio operativo degli intermediari bancari ed assicurativi, a partire dagli aspetti regolamentari, passando per quelli gestionali fino ad arrivare al tema centrale: la misurazione del rischio. Questa viene affrontata prima tramite un’approfondita review della letteratura, poi sviluppando una proposta di modello di misurazione, utilizzabile da ogni intermediario che cerchi di coniugare da una parte le esigenze di semplicità e comparabilità, dall’altra quelle di robustezza, tutte richieste anche dal regolatore.
A tale scopo viene assemblato un particolare database, contenente i dati perdita operativa di entrambe le tipologie di intermediari, bancari ed assicurativi, in modo da riuscire a cogliere le caratteristiche comuni. La metodologia seguita è quella del Loss Distribution Approach, con le distribuzioni di Poisson e Log-normale rispettivamente per frequenza ed impatto, secondo le best practice di mercato.
Il contributo innovativo è rappresentato dalla modalità con cui si giunge alla misura di rischio operativo complessiva: solitamente, infatti, l’analisi delle perdite operative avviene all’interno di sottocategorie di rischio, e per la misura aggregata si calcola la semplice somma delle singole misure; tale procedimento, sebbene incoraggiato dal normatore di vigilanza bancaria in ottica prudenziale, non consente di cogliere in modo adeguato la rischiosità effettiva: su questa tematica viene svolto il secondo approfondimento, ed all’aggregazione dei rischi si guarda ancora dalla prospettiva regolamentare, letteraria, implementativa.
L’aggregazione pone la questione delle dipendenze tra i rischi in esame: un’analisi preliminare indaga le relazioni tra perdite operative e variabili macroeconomiche, senza però confermare la predittività di tali fattori, quindi le correlazioni vengono ricavate direttamente a partire dai dati storici di perdita. Infine la metodologia utilizza lo strumento delle copule, che permette di tenere conto delle dipendenze di coda, caratteristica peculiare del rischio operativo ed emergente ancor di più nei periodi di stress; i risultati vedono emergere un beneficio da diversificazione non trascurabile, in linea con i rarissimi contributi della letteratura sul tema
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