1,721,122 research outputs found

    Common and divergent molecular mechanisms of fasting and ketogenic diets

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    Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality

    Simultaneous single neuron recording of O2 consumption, [Ca2+]i and mitochondrial membrane potential in glutamate toxicity

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    In order to determine the sequence of cellular processes in glutamate toxicity, we simultaneously recorded O(2) consumption, cytosolic Ca(2+) concentration ([Ca(2+)](i)), and mitochondrial membrane potential (mDeltapsi) in single cortical neurons. Oxygen consumption was measured using an amperometric self-referencing platinum electrode adjacent to neurons in which [Ca(2+)](i) and mDeltapsi were monitored with Fluo-4 and TMRE(+), respectively, using a spinning disk laser confocal microscope. Excitotoxic doses of glutamate caused an elevation of [Ca(2+)](i) followed seconds afterwards by an increase in O(2) consumption which reached a maximum level within 1-5 min. A modest increase in mDeltapsi occurred during this time period, and then, shortly before maximal O(2) consumption was reached, the mDeltapsi, as indicated by TMRE(+) fluorescence, dissipated. Maximal O(2) consumption lasted up to 5 min and then declined together with mDeltapsi and ATP levels, while [Ca(2+)](i) further increased. mDeltapsi and [Ca(2+)](i) returned to baseline levels when neurons were treated with an NMDA receptor antagonist shortly after the [Ca(2+)](i) increased. Our unprecedented spatial and time resolution revealed that this sequence of events is identical in all neurons, albeit with considerable variability in magnitude and kinetics of changes in O(2) consumption, [Ca(2+)](i), and mDeltapsi. The data obtained using this new method are consistent with a model where Ca(2+) influx causes ATP depletion, despite maximal mitochondrial respiration, minutes after glutamate receptor activation

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Mitochondrial Quality Control as a Therapeutic Target.

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    In addition to oxidative phosphorylation (OXPHOS), mitochondria perform other functions such as heme biosynthesis and oxygen sensing and mediate calcium homeostasis, cell growth, and cell death. They participate in cell communication and regulation of inflammation and are important considerations in aging, drug toxicity, and pathogenesis. The cell's capacity to maintain its mitochondria involves intramitochondrial processes, such as heme and protein turnover, and those involving entire organelles, such as fusion, fission, selective mitochondrial macroautophagy (mitophagy), and mitochondrial biogenesis. The integration of these processes exemplifies mitochondrial quality control (QC), which is also important in cellular disorders ranging from primary mitochondrial genetic diseases to those that involve mitochondria secondarily, such as neurodegenerative, cardiovascular, inflammatory, and metabolic syndromes. Consequently, mitochondrial biology represents a potentially useful, but relatively unexploited area of therapeutic innovation. In patients with genetic OXPHOS disorders, the largest group of inborn errors of metabolism, effective therapies, apart from symptomatic and nutritional measures, are largely lacking. Moreover, the genetic and biochemical heterogeneity of these states is remarkably similar to those of certain acquired diseases characterized by metabolic and oxidative stress and displaying wide variability. This biologic variability reflects cell-specific and repair processes that complicate rational pharmacological approaches to both primary and secondary mitochondrial disorders. However, emerging concepts of mitochondrial turnover and dynamics along with new mitochondrial disease models are providing opportunities to develop and evaluate mitochondrial QC-based therapies. The goals of such therapies extend beyond amelioration of energy insufficiency and tissue loss and entail cell repair, cell replacement, and the prevention of fibrosis. This review summarizes current concepts of mitochondria as disease elements and outlines novel strategies to address mitochondrial dysfunction through the stimulation of mitochondrial biogenesis and quality control

    Variations on the Author

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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