1,720,967 research outputs found
The role of calcium homeostasis in mitochondrial diseases and neurodegeneration
Full text linkCa2+ is one of the main second messengers of cells and, in particular the Ca2+ signaling in mitochondria is involved in different physiological processes spanning from cell metabolism, through the control of mitochondrial respiration and crucial metabolic enzymes, to the response in stress conditions.
Despite the lack of a mechanistic understanding, it is well known that mitochondrial Ca2+ overload is the most important trigger for the opening of permeability transition pore responsible for apoptosis induction after several toxic challenges. On the contrary, the role of Ca2+ signaling in autophagy only recently started to emerge. Autophagy is a process of self-eating by which cellular organelles and proteins are sequestered and degraded in order to produce energy and amino acids in metabolic stress conditions, such as nutrient deprivation. It is not surprising that mitochondrial Ca2+ also plays an important role in the pathological alteration of cell physiology in different human disorders.
In the present work we will consider, in particular, the involvement of mitochondrial Ca2+ homeostasis and its correlated metabolic processes in two models of human diseases: mitochondrial disorders and neurodegeneration.
Mitochondrial disorders are a large group of heterogeneous diseases, commonly defined by a lack of cellular energy due to oxidative phosphorylation defects. We used skin primary fibroblasts derived from a patient with a complex I mutation in ND5 subunit, as a model of mitochondrial disorders. This system revealed an interesting correlation between the decrease in mitochondrial Ca2+ uptake and the increase in autophagic flux. In addition, our results suggest that this is due to a structural rearrangement of intracellular organelle architecture causing a loss of ER-mitochondria contact sites.
Neurodegeneration is caused by selective and progressive death of specific neuronal subtypes. In order to understand the involvement of mitochondrial Ca2+ signaling in the pathogenesis of neurodegeneration, we developed an in vitro system of mouse primary cortical neurons and we optimized an in vivo model of microinjection in mouse brain regions. In particular, we studied the effect of an increased mitochondrial Ca2+ uptake, induced by the overexpression of mitochondrial Ca2+ uniporter (MCU, the main responsible of Ca2+ entry in mitochondrial matrix), on cell survival, in both primary cultures and in midbrain mouse area. We concluded that mitochondrial Ca2+ accumulation induces mitochondrial fragmentation and higher sensitivity to cell death in neurons both in vitro and in viv
Molecules and roles of mitochondrial calcium signaling
No full textMitochondrial Ca(2+) homeostasis is an important component of the calcium-mediated cellular response to extracellular stimuli. It controls key organelle functions, such as aerobic metabolism and the induction of apoptotic cell death, and shapes the spatiotemporal pattern of the cytosolic [Ca(2+)] increase. We here summarize both the main roles of Ca(2+) signals within mitochondria and the emerging molecular information that is starting to unravel the composition of the signaling apparatus and reveal potential pharmacological targets in this process of utmost pathophysiological relevance
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
- …
