1,720,959 research outputs found
The human extended mitochondrial metabolic network: New hubs from lipids
No full textEven if systems thinking is not new in biology, rationalizing the explosively growing amount of knowledge
has been the compelling reason for the sudden rise and spreading of systems biology. Based on ‘omics’
data, several genome-scale metabolic networks have been reconstructed and validated. One of the most
striking aspects of complex metabolic networks is the pervasive power-law appearance of metabolite
connectivity. However, the combinatorial diversity of some classes of compounds, such as lipids, has been
scarcely considered so far. In this work, a lipid-extended human mitochondrial metabolic network has
been built and analyzed. It is shown that, considering combinatorial diversity of lipids and multipurpose
enzymes, an intimate connection between membrane lipids and oxidative phosphorilation appears. This
finding leads to some biomedical considerations on diseases involving mitochondrial enzymes. Moreover,
the lipid-extended network still shows power-law features. Power-law distributions are intrinsic
to metabolic network organization and evolution. Hubs in the lipid-extended mitochondrial network
strongly suggest that the “RNA world” and the “lipid world” hypothesis are both correct
Amyloid beta(1–42) in aqueous environments: Effects of ionic strength and E22Q (Dutch) mutation
No full textDevelopment of extracellular plaques characteristic of Alzheimer’s disease is related to aggregation of amyloid peptides. The Aβ-42 peptide is the most aggregation prone species, and some missense mutant forms increase this aggregation ability. Due to its poor solubility as monomer in aqueous solutions, Aβ-42 conformational transitions in water have been largely investigated by molecular dynamics. Here we report an all-atom molecular dynamics analysis of the Aβ-42 peptide in aqueous environment using as starting conformation a structure obtained in an isotropic, low-polarity medium, representing a plausible model for the membrane-bound species. While previous studies commonly show that Aβ-42 is largely unstructured in aqueous solution, here we report that this peptide can adopt partially folded structures. Importance of ionic strength has been also investigated, showing that at physiological ionic strength condition a loop stabilizing electrostatic interaction involving Lys28 builds-up. In addition, beside stable α-helix structures, we observe the appearance of 310 helix, similar to what reported experimentally for the Aβ-40 species. The effect of E22Q (Dutch) mutation in high ionic strength condition has been explored. We show that this mutation has a dramatic impact on the Aβ-42 structure. Instead of a partially folded, but extended, conformation obtained with the wild type, the E22Q assumes a two-helix collapsed one due to the clustering of hydrophobic residues
Molecular dynamics in cytochrome c oxidase Mössbauer spectra deconvolution
No full textIn this work low temperature molecular dynamics simulations of cytochrome c oxidase are used to predict an experimentally observable, namely Mössbauer spectra width. Predicted lineshapes are used to model Lorentzian doublets, with which published cytochrome c oxidase Mössbauer spectra were simulated. Molecular dynamics imposed constraints to spectral lineshapes permit to obtain useful information, like the presence of multiple chemical species in the binuclear center of cytochrome c oxidase. Moreover, a benchmark of quality for molecular dynamic simulations can be obtained. Despite the overwhelming importance of dynamics in electron-proton transfer systems, limited work has been devoted to unravel how much realistic are molecular dynamics simulations results. In this work, molecular dynamics based predictions are found to be in good agreement with published experimental spectra, showing that we can confidently rely on actual simulations. Molecular dynamics based deconvolution of Mössbauer spectra will lead to a renewed interest for application of this approach in bioenergetics
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
Prediction of high- and low-affinity quinol-analogue-binding sites in the aa(3) and bo(3) terminal oxidases from Bacillus subtilis and Escherichia coli
No full textHaem–copper oxidases are the terminal enzymes in both prokaryotic and eukaryotic respiratory chains. They catalyse the reduction of dioxygen to water and convert redox energy into a transmembrane electrochemical proton gradient during their catalytic activity. Haem–copper oxidases show substantial structure similarity, but spectroscopic and biochemical analyses indicate that these enzymes contain diverse prosthetic groups and use different substrates (i.e. cytochrome c or quinol). Owing to difficulties in membrane protein crystallization, there are no definitive structural data about the quinol oxidase physiological substrate-binding site(s). In the present paper, we propose an atomic structure model for the menaquinol:O2 oxidoreductase of Bacillus subtilis (QOx.aa3). Furthermore, a multistep computational approach is used to predict residues involved in the menaquinol/menaquinone binding within B. subtilis QOx.aa3 as well as those involved in quinol/quinone binding within Escherichia coli QOx.bo3. Two specific sequence motifs, R70GGXDX4RXQX3PX3FX[D/N/E/Q]X2HYNE97 and G159GSPX2GWX2Y169 (B. subtilis numbering), were highlighted within QOx from Bacillales. Specific residues within the first and the second sequencemotif participate in the high- and low-affinity substrate-binding sites respectively. Using comparative analysis, two analogous motifs, R71GFXDX4RXQX8[Y/F]XPPHHYDQ101 and G163EFX3GWX2Y173 (E. coli numbering) were proposed to be involved in Enterobacteriales/Rhodobacterales/Rhodospirillales QOx high- and low-affinity quinol-derivative-binding sites. Results and models are discussed in the context of the literature
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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