1,720,966 research outputs found
Regolazione Parkin-dipendente delle componenti del complesso dell’Uniporto Mitocondriale del Calcio
Full text linkIl complesso dell’Uniporto Mitocondriale del Calcio è una struttura multiproteica composta dal canale selettivo al calcio (MCU) e da una serie di proteine accessorie, tra cui MICU1, MICU2 ed EMRE. L’attività integrata e sinergica di queste proteine, presenti a livello della membrana mitocondriale interna, è fondamentale per la sottile regolazione dell’ingresso del calcio nella matrice mitocondriale al fine di sostenere la bioenergetica cellulare e regolare la risposta apoptotica. Allo scopo di assolvere questi compiti anche il turnover cellulare di tutte le componenti del complesso deve essere altamente regolato in modo da evitare l’instaurarsi di condizioni patologiche associate alla deregolazione del calcio mitocondriale; i meccanismi coinvolti nella degradazione di queste proteine mitocondriali non sono ancora noti.
Questo lavoro di tesi ha messo alla luce una degradazione rapida e selettiva di MICU1, regolatore positivo del complesso dell’Uniporto Mitocondriale del Calcio, da parte del sistema di degradazione citosolico Ubiquitina-Proteasoma (UPS). Come potenziale candidato coinvolto in questa regolazione viene identificata la E3 ubiquitina-ligasi Parkin (PARK2), le cui mutazioni sono causa di forme autosomiche recessive ad insorgenza precoce di Parkinson. A sostegno di ciò l’overespressione di Parkin induce una netta diminuzione dei livelli basali di MICU1. I risultati ottenuti evidenziano inoltre un’interazione fisica tra Parkin e MICU1 ed è interessante notare che la presenza del dominio Ubl sembra essere fondamentale per la degradazione di questo regolatore di MCU suggerendone il coinvolgimento nei meccanismi di autoinibizione basale di Parkin.
I dati sostengono quindi un modello in cui Parkin, l’E3 ubiquitina-ligasi associata al Parkinson, è coinvolta nella degradazione selettiva di MICU1, questa regolazione contribuisce alla modulazione dei segnali mitocondriali di calcio evidenziando come alterazioni nella capacità dei mitocondri di captare calcio possono contribuire all’insorgenza del Parkinson.The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by the Ca2+selective pore-forming subunit mitochondrial uniporter (MCU) and accessory proteins, including MICU1, MICU2 and EMRE. Their concerted action at the inner mitochondrial membrane is required to fine-tune the uptake of Ca2+ into the matrix to sustain cell bioenergetics and to regulate the apoptotic response. To fulfill such requirements, and to avoid the many cell-type dependent pathological conditions associated with impaired mitochondrial Ca2+ handling, the intracellular turnover of all the components must also be tightly regulated. However, the mechanism(s) and the players involved in this process are still unknown. This work shows that the MCU complex regulator MICU1 is rapidly and selectively turned-over by the Ubiquitin Proteasome System (UPS). Moreover, the multifunctional E3 ubiquitin ligase Parkin (PARK2), whose mutations cause autosomal recessive early-onset Parkinson’s disease (PD), was identified as a potential candidate involved in this regulation since its upregulation strongly decreases the MICU1 basal levels. Parkin was also found to interact with MICU1 and, interestingly, the presence of the Ubl-domain is required for the Parkin-mediated degradation of MICU1, suggesting that it may play a role in the basal auto-inhibited state. These findings support a model in which the PD-related E3 ubiquitin ligase Parkin participates in the selective regulation of the MCU complex regulator MICU1, thus contributing to shape the mitochondrial Ca2+ signals and supporting the notion that impairments in the ability of mitochondria to take up Ca2+ might contribute to the pathogenesis of PD
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
Effects of ticagrelor on the sodium/calcium exchanger 1 (NCX1) in cardiac derived H9c2 cells
No full textTicagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Clinical effects of ticagrelor cannot be simply accounted for by pure platelet inhibition, and off-target mechanisms can potentially play a role. In particular, recent evidence suggests that ticagrelor may also influence heart function and improve the evolution of myocardial ischemic injury by more direct effects on myocytes. The cardiac sodium/calcium exchanger 1 (NCX1) is a critical player in the generation and control of calcium (Ca2+) signals, which orchestrate multiple myocyte activities in health and disease. Altered expression and/or activity of NCX1 can have profound consequences for the function and fate of myocytes. Whether ticagrelor affects cardiac NCX1 has not been investigated yet. To explore this hypothesis, we analyzed the expression, localization and activity of NCX1 in the heart derived H9c2-NCX1 cells following ticagrelor exposure. We found that ticagrelor concentration- and time-dependently reduced the activity of the cardiac NCX1 in H9c2 cells. In particular, the inhibitory effect of ticagrelor on the Ca2+-influx mode of NCX1 was evident within 1 h and further developed after 24 h, when NCX1 activity was suppressed by about 55% in cells treated with 1 μM ticagrelor. Ticagrelor-induced inhibition of exchanger activity was reached at clinically relevant concentrations, without affecting the expression levels and subcellular distribution of NCX1. Collectively, these findings suggest that cardiac NCX1 is a new downstream target of ticagrelor, which may contribute to the therapeutic profile of ticagrelor in clinical practice
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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