1,721,028 research outputs found
nutrient dependent control of mitochondrial Ca2+ signaling
Full text linkEukaryotic cells are able to continuously adapt to fluctuations in external conditions. Furthermore, when metabolites availability varies, cells undergo rapid changes in order to adapt their metabolism and protect themselves against potential damages. These rapid changes are regulated through different nutrient dependent pathways. The most important proteins, known so far, involved in these pathways are AMPK and Sirtuins. These proteins, that have a key role in the cells response to caloric stress, are activated when the cells are under nutrient deprivation (Dilova et al. 2007).
Ca2+ is a fundamental second messenger that enters the cytosol upon the opening of a variety of plasma membrane and endoplasmic/sarcoplasmic reticulum (ER/SR) channels and controls numerous cell functions also at the mitochondrial site (Rizzuto and Pozzan 2006). Foskett’group recently identified a new role of constitutive Ca2+ transfer from ER to mitochondria. They demonstrated that this represents a crucial intracellular signal for AMPK activation and autophagy induction. On the other hand still unknown are the precise physiological signals inside the cell that can translate fluctuation of metabolites concentration into a specific regulation of mitochondrial Ca2+ content (Cardenas et al. 2010).
During my PhD, I measured mitochondrial Ca2+ uptake using targeted recombinant aequorin (Pinton et al. 2007). I found that in HeLa cells, after 2 hours of glucose deprivation, mitochondrial Ca2+ uptake is drastically reduced. This physiological response appears to be transient and reversible. Indeed, after glucose deprivation, cells show a reduced mitochondrial Ca2+ uptake up to 4 hours, but after this period it returns to the levels measured in normal feeding conditions. I also investigated the possible involvement of a newly identified regulator of mitochondria Ca2+ uptake, MICU1, and we found that after 2 hours of glucose deprivation this regulator is quickly degraded. Based on its short half-life, we wondered whether during glucose deprivation MICU1 could be ubiquitylated and rapidly degraded. I also found that the proteasome inhibitor MG132 inhibits MICU1 degradation during glucose deprivation and it also increases MICU1 half-life. High-resolution mass spectrometry data reveal five lysines in MICU1 protein sequence that are reported to be ubiquitylated. Thus, I decided to substitute each one of these lysines with one arginine (K>R) in order to generate a MICU1 ubiquitylation incompetent mutant (MICU1K102R, K103R, K104R, K296R, K359R). Importantly, I found that the overexpression of MICU1K102R, K103R, K104R, K296R, K359R partially abolishes the effect of glucose deprivation on mitochondrial Ca2+ uptake. Further experiments will allow us to understand how MICU1 influences the modulation of the activity of mitochondrial Ca2+ transport system. The analysis of this mechanism will allow us to understand if mitochondria can be the link that directly connects glucose availability with the modulation of physio-pathological processes such as autophagy and apoptosis
Structure and function of the mitochondrial calcium uniporter complex.
No full textAbstractThe mitochondrial calcium uniporter (MCU) is the critical protein of the inner mitochondrial membrane mediating the electrophoretic Ca2+ uptake into the matrix. It plays a fundamental role in the shaping of global calcium signaling and in the control of aerobic metabolism as well as apoptosis. Two features of mitochondrial calcium signaling have been known for a long time: i) mitochondrial Ca2+ uptake widely varies among cells and tissues, and ii) channel opening strongly relies on the extramitochondrial Ca2+ concentration, with low activity at resting [Ca2+] and high capacity as soon as calcium signaling is activated. Such complexity requires a specialized molecular machinery, with several primary components can be variably gathered together in order to match energy demands and protect from toxic stimuli. In line with this, MCU is now recognized to be part of a macromolecular complex known as the MCU complex. Our understanding of the structure and function of the MCU complex is now growing promptly, revealing an unexpected complexity that highlights the pleiotropic role of mitochondrial Ca2+ signals. This article is part of a Special Issue entitled: 13th European Symposium on Calcium
Withdrawal of essential amino acids increases autophagy by a pathway involving Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β).
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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
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