1,720,988 research outputs found
EXPRESSION MODULATION OF A SMALL HEAT SHOCK PROTEIN INVOLVED IN NEURODEGENERATIVE DISEASES
No full text
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
L’inibizione dell’attività ATPasica della dineina riduce l’aggregazione del recettore degli androgeni mutato responsabile dell’ Atrofia Muscolare Spinale e Bulbare (SBMA)
No full textTra le Malattie del Motoneurone, l’Atrofia Muscolare Spinale e Bulbare (SBMA) ha assunto un particolare interesse. Tale malattia è legata al cromosoma X ed è dovuta all’espansione della sequenza CAG presente nel primo esone del gene che codifica per il recettore androgenico (AR). Tale espansione nucleotidica codifica per una sequenza poliQ che porta l’AR-poliQ ad assumere conformazioni aberranti (misfolding). L’interesse per questa malattia risiede nel fatto che la tossicità dell’AR-poliQ è strettamente dipendente dal suo ligando testosterone. Questo steroide induce il misfolding dell’AR che così tende a formare aggregati, capaci di sregolare il sistema di controllo di qualità proteico e saturare i sistemi ubiquitina proteasoma e/o autofagico.
L’autofagia richiede il trasporto, mediato dalla dineina, delle proteine misfoldate verso il centro di organizzazione dei microtubuli, ove, si ha la formazione dell’autofagosoma. Successivamente la dineina partecipa al trasporto dell’autofagosoma mediandone la fusione con il lisosoma.
In immunofluorescenza abbiamo dimostrato che la dineina è sequestrata all’interno degli aggregati di AR misfoldato (GFP-ARQ.48) indotti dal testosterone. Abbiamo utilizzato EHNA, un inibitore selettivo della funzione ATPasica della dineina per impedirne il suo movimento lungo i microtubuli e valutato alterazioni dell’aggregazione testosterone dipendente dell’AR. E’ stata quantificata la presenza di aggregati proteici PBS insolubili di AR wild type e poliQ in presenza del blocco del trasporto mediato dalla dineina. I risultati mostrano una netta riduzione degli aggregati proteici citoplasmatici di ARQ.46 indotti dal testosterone, lasciando inalterati i livelli di AR-poliQ in assenza dell’ormone. Invece, EHNA non ha ridotto gli aggregati proteici nucleari di ARQ.112 indotti da testosterone, ma esclusivamente la quota basale di proteina aggregata in assenza dell’ormone. Questi dati indicano che il meccanismo di trasporto mediato dalla dineina svolge un ruolo chiave nella formazione degli aggregati di AR-poliQ indotti dal testosterone e accumulati nella SBMA, è quindi un possibile target terapeutico della patologia
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
Inhibition of dynein ATPase activity reduces aggregation of misfolded proteins involved in motoneuron diseases
No full textSpinobulbar muscular atrophy and amyotrophic lateral sclerosis are two motor neuron diseases (MNDs) characterized by selective death of motor neuron localized in cerebral cortex and in spinal cord. The hallmark of SBMA and ALS is the presence of aggregates of mutant proteins (androgen receptors (AR) and superoxide dismutase 1(SOD1), TDP43, etc. respectively) with aberrant conformation (misfolding). Altered protein quality control system cannot correctly remove toxic aggregates of misfolding proteins. These species may lead to cell death. Dynein motor complex seems play a crucial role to maintain an efficient removal of these toxic species by autophagy: i) through aggregate transport near MTOC, ii) by autophagosome nucleation, iii) by assisting the fusion of autophagosome to lysosome.
Treatment of NSC34 cell line with a selective inhibitor of dynein (EHNA), drastically reduce the autophagy marker LC3 when autophagy is induced by trehalose. In NSC34 transfected with mutant proteins: i) immunofluorescence (IF) analysis showed that dynein is sequestered into mutant AR aggregates. ii) EHNA treatment, unexpectedly, reduces aggregates of mutant AR, SOD1 and TDP43 retained on cellulose acetate membrane in filter retardation assay (FTA) also in presence of autophagy inhibitor (3-MA), but not in presence of proteasome inhibitor (MG132). iii) EHNA increases the solubility of mutated AR. iv) BAG1, which routes misfolding proteins to proteasome degradation or chaperone-mediated-autophagy, is increases after EHNA treatment.
These data suggest that dynein impairment may induces proteasome targeting of misfolded proteins involve in MNDs
BAG3-mediated rerouting of proteasomal clients towards autophagy upon proteasomal impairment
No full textThe accumulation of misfolded, mutant proteins is a common basis for many adult onset neurodegenerative diseases. Cells have evolved an elaborate protein quality control system, which acts to facilitate the folding or refolding of misfolded protein species by molecular chaperones or, if folding is unsuccessful, these same chaperones often target the misfolded proteins for degradation, thereby preventing protein aggregation. Intracellular degradation is primarily mediated by two proteolytic systems: the autophagy and the ubiquitin proteasomal systems. Proteotoxic stress can lead to proteasomal impairment and augmented authophagosomal capacity in order to ensure proper clearance of clients (proteasome-autophagy switch). However, neither the mechanism of sensing nor that of switching is understood. Here, we show that after proteasome inhibition, BAG-3 is upregulated and is a major executor of the proteasome-autophagy switch. BAG-3 both boosts autophagy and redirects HSP70-bound proteasomal clients to autophagosomes through competitive inhibition with its family member BAG-1, that normally directs HSP70-bound clients to the proteasome, thus playing a key role in the maintenance of protein homeostasis under proteotoxic stress conditions.
GRANTS: Telethon | Fondazione CARIPLO | AriSLA | Fondazione Thierry Latran | Ministero della Salute | National Ataxia Foundation | Marie Curie Action | Prinses Beatrix Fond
- …
