1,720,992 research outputs found
Nicotinamide Nucleotide Transhydrogenase as a Sensor of Mitochondrial Biology
Full text linkThe enzyme nicotinamide nucleotide transhydrogenase (NNT) transfers hydride from NADH to NADP+ coupled to H+ translocation across the inner mitochondrial membrane. In a recent study, Kampjut and Sazanov reveal that the bifunctional NNT mechanism rules the NAD(P)+/NAD(P)H interconversion ratio, which in turn regulates antioxidant defense and sirtuin actions
Organotin effects in different Phyla: discrepancies and similarities
No full textMost of the biological effects displayed by organotin contaminants, among which trisubsituted species are especially toxic, have increasingly been found to exhibit astonishing analogies in different taxa. While similarities can be perceived from prokaryotes to mammals, different modes and extent of biochemical and biological effects were described in different cells, tissues and species. A broad susceptibility range to organotins emerges from literature. Aquatic biota are mainly affected by organotins as environmental water and sediments act as storage site. Endocrine and lipid homeostasis perturbations span from Mollusks, where first gender changes (imposex) referable to environmental organotin contamination was pointed out, to Mammals, where organotins play the role of environmental obesogens. Organotin immunotoxicity, elicited in various invertebrate Phyla, also affects humans. Inhibition of key membrane-bound enzyme complexes such as Na,K-ATPase and FOF1 complexes, thus affecting hydromineral balance, energy production and related effects, are known to occur in a wide variety of organisms. Mitochondria and all membrane functions apparently represent a preferred target of these lipophilic toxicants. Highly conserved action mechanisms could be involved in the observed effects: organotin binding to nuclear receptors, membrane components and intracellular proteins as well as DNA damage may represent widely shared action modes of these compounds. On the other hand the different response and even the refractoriness to these toxicants shown at different biological levels may mirror biochemical and physiological selectivity of signalling pathways, biomembranes and intracellular protein components
A Therapeutic Role for the F1FO-ATP Synthase
Full text linkRecently, the F1FO-ATP synthase, due to its dual role of life enzyme as main adenosine triphosphate (ATP) maker and of death enzyme, as ATP dissipator and putative structural component of the mitochondrial permeability transition pore (mPTP), which triggers cell death, has been increasingly considered as a drug target. Accordingly, the enzyme offers new strategies to counteract the increased antibiotic resistance. The challenge is to find or synthesize compounds able to discriminate between prokaryotic and mitochondrial F1FO-ATP synthase, exploiting subtle structural differences to kill pathogens without affecting the host. From this perspective, the eukaryotic enzyme could also be made refractory to macrolide antibiotics by chemically produced posttranslational modifications. Moreover, because the mitochondrial F1FO-ATPase activity stimulated by Ca2+ instead of by the natural modulator Mg2+ is most likely involved in mPTP formation, effectors preferentially targeting the Ca2+-activated enzyme may modulate the mPTP. If the enzyme involvement in the mPTP is confirmed, Ca2+-ATPase inhibitors may counteract conditions featured by an increased mPTP activity, such as neurodegenerative and cardiovascular diseases and physiological aging. Conversely, mPTP opening could be pharmacologically stimulated to selectively kill unwanted cells. On the basis of recent literature and promising lab findings, the action mechanism of F1 and FO inhibitors is considered. These molecules may act as enzyme modifiers and constitute new drugs to kill pathogens, improve compromised enzyme functions, and limit the deathly enzyme role in pathologies. The enzyme offers a wide spectrum of therapeutic strategies to fight at the molecular level diseases whose treatment is still insufficient or merely symptomatic
Failure localization through progressive network tomography
No full textBoolean Network Tomography (BNT) allows to localize network failures by means of end-to-end monitoring paths. Nevertheless, it falls short of providing efficient failure identification in real scenarios, due to the large combinatorial size of the solution space, especially when multiple failures occur concurrently. We aim at maximizing the identification capabilities of a bounded number of monitoring probes. To tackle this problem we propose a progressive approach to failure localization based on stochastic optimization, whose solution is the optimal sequence of monitoring paths to probe. We address the complexity of the problem by proposing a greedy strategy in two variants: one considers exact calculation of posterior probabilities of node failures given the observation, whereas the other approximates these values through a novel failure centrality metric. We discuss the approximation of the proposed approaches. Then, by means of numerical experiments conducted on real network topologies, we demonstrate the practical applicability of our approach. The performance evaluation evidences the superiority of our algorithms with respect to state of the art solutions based on classic Boolean Network Tomography as well as approaches based on sequential group testing
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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