1,721,033 research outputs found
Use of bacterial photosynthetic vesicles to evaluate the effect of ionic liquids on the permeability of biological membranes
Full text link: Ionic liquids (ILs) are salts composed of a combination of organic or inorganic cations and anions characterized by a low melting point, often below 100 °C. This property, together with an extremely low vapor pressure, low flammability and high thermal stability, makes them suitable for replacing canonical organic solvents, with a reduction of industrial activities impact on the environment. Although in the last decades the eco-compatibility of ILs has been extensively verified through toxicological tests performed on model organisms, a detailed understanding of the interaction of these compounds with biological membranes is far from being exhaustive. In this context, we have chosen to evaluate the effect of some ILs on native membranes by using chromatophores, photosynthetic vesicles that can be isolated from Rhodobacter capsulatus, a member of the purple non‐sulfur bacteria. Here, carotenoids associated with the light-harvesting complex II, act as endogenous spectral probes of the transmembrane electrical potential (ΔΨ). By measuring through time-resolved absorption spectroscopy the evolution of the carotenoid band shift induced by a single excitation of the photosynthetic reaction center, information on the ΔΨ dissipation due to ionic currents across the membrane can be obtained. We found that some ILs cause a rather fast dissipation of the transmembrane ΔΨ even at low concentrations, and that this behavior is dose-dependent. By using two different models to analyze the decay of the carotenoid signals, we attempted to interpret at a mechanistic level the marked increase of ionic permeability caused by specific ILs
Mitochondrial Respiratory Supercomplexes in Physiology and Diseases
No full textIn eukaryotic cells, mitochondria play the fundamental role of ATP production during the
process of oxidative phosphorylation (OXPHOS). However, these cytosolic organelles also
have several other important physiological functions, including sugar and fatty acid catabo-
lism, amino acid metabolism, buffering of the cytosolic calcium concentration (Rizzuto
et al., 2012), regulation and execution of different types of cell death (Galluzzi et al., 2012)
and arrangement of adaptive responses to perturbations of intracellular homeostasis (Liesa
and Shirihai, 2013). Furthermore, mitochondria are able to discharge a range of intracel-
lular signals including reactive oxygen species (ROS), mitochondrial DNA (mtDNA) and
specific proteins, thus operating as fundamental hubs of a wide array of signalling pathways
(Galluzzi et al., 2012)
Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution
Full text linkSummary: Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit. Downregulation of Drp1 rescued the lethality and bioenergetic defect caused by neuronal Marf RNAi, but induced only a modest restoration of axonal mitochondria distribution. Surprisingly, Drp1 knockdown rescued fragmentation and fully restored aberrant distribution of axonal mitochondria produced by Opa1 RNAi; however, Drp1 knockdown did not improve viability or mitochondria function. Our data show that proper morphology is critical for proper axonal mitochondria distribution independent of bioenergetic efficiency. The health of neurons largely depends on mitochondria function, but does not depend on shape or distribution. : Trevisan et al. separate the independent contribution of form and function in determining the distribution of mitochondria in axons. They show that morphology is crucial for proper axonal mitochondria distribution, independent of their bioenergetic efficiency. However, the health of neurons depends on mitochondria function, but does not depend on shape or distribution
Complex II phosphorylation is triggered by unbalanced redox homeostasis in cells lacking complex III
No full textA marked stimulation of complex II enzymatic activity was detected in cybrids bearing a homoplasmic MTCYB microdeletion causing disruption of both the activity and the assembly of complex III, but not in cybrids harbouring another MTCYB mutation affecting only the complex III activity. Moreover, complex II stimulation was associated with SDHA subunit tyrosine phosphorylation. Despite the lack of detectable hydrogen peroxide production, up-regulation of the levels of mitochondrial antioxidant defenses revealed a significant redox unbalance. This effect was also supported by the finding that treatment with N-acetylcysteine dampened the complex II stimulation, SDHA subunit tyrosine phosphorylation, and levels of antioxidant enzymes. In the absence of complex III, the cellular amount of succinate, but not fumarate, was markedly increased, indicating that enhanced activity of complex II is hampered due to the blockage of respiratory electron flow. Thus, we propose that complex II phosphorylation and stimulation of its activity represent a molecular mechanism triggered by perturbation of mitochondrial redox homeostasis due to severe dysfunction of respiratory complexes. Depending on the site and nature of the damage, complex II stimulation can either bypass the energetic deficit as an efficient compensatory mechanism, or be ineffectual, leaving cells to rely on glycolysis for survival
Inherited optic neuropathies: working on mitochondrial bioenergetics and dynamics to discover new therapeutic strategies
Full text linkInherited optic neuropathies are neurodegenerative disorders characterized by mitochondrial dysfunctions. Leber’s Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA) are caused by mutations in respiratory complex I (CI) core subunits and OPA1 mutations, respectively and there is no established cure. For LHON the only approved drug is idebenone but its antioxidant effects depend on its reduced form feeding electrons to CIII. NAD(P)H-quinone dehydrogenase (NQO1), an inducible cytosolic enzyme, is involved in the antioxidant response through reduction of quinones, though clear evidence about its role is still lacking. DOA is caused by mutations in OPA1 gene encoding a mitochondrial GTPase involved in mitochondrial functions. First, we show that in LHON cellular models overexpressing NQO1, idebenone treatment rescues rotenone-sensitive mitochondrial respiration and ATP synthesis, as well as reducing ROS production. This demonstrates NQO1 supports oxidative phosphorylation bypassing CI and directly transfers electrons to CIII via the NQO1-idebenone-CIII pathway. Indeed, only patient-derived fibroblasts expressing NQO1 are able to maintain respiration. Finally, treatment with NQO1 inducer dimethyl fumarate allows mitochondrial respiration in the presence of idebenone, demonstrating the correlation between NQO1 expression and the efficacy of idebenone. Subsequently, we aim to validate FDA-approved molecules, “OPA1 rescuing molecules” (ORMs), able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. Here, we show the testing of six selected compounds in Opa1-ablated mouse embryonic fibroblasts (MEFs) expressing the human OPA1 isoform1 bearing the R445H and D603H mutations. Some of these molecules ameliorate the bioenergetics and/or the mitochondrial morphology, depending on the mutation. ORM14 is the most effective compound showing both energy and morphology rescuing in the final validation on patient-derived fibroblasts. Our results permit the translation into clinic of the biochemical findings on the role of NQO1 for LHON treatment, as well as “drug repurposing” for DOA
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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