1,720,960 research outputs found
Investigating the ferroportin-ferroxidase system
Full text linkIron is essential for various pivotal biological processes, such as oxygen transport, DNA synthesis, and ATP production. In humans, dysregulation in iron metabolism leads to severe disorders due to its intrinsic toxicity. Thus, iron homeostasis has to be tightly regulated to ensure its safe handling.
A crucial role in recycling and systemic iron homeostasis is played by a system formed by the unique iron transporter ferroportin and a ferroxidase, that mediate safe export of iron across cellular membranes. Despite its importance, several aspects of this system still have to be unveiled. This work focuses on addressing different unanswered questions of the iron export mechanism.
The precise modality in which the transporter ferroportin operates is still under debate. To enable its systematic characterization, site-specific fluorescent labeled versions of FPN were generated. Employing the genetic incorporation of unnatural amino acid technique we successfully incorporated the fluorescent probe dansylalanine in four different positions within the structure of the transporter. Fluorescence spectroscopy confirmed the ability of the fluorophore to sense conformational changes upon metal binding by ferroportin. Thus, a reliable experimental system to systematically probe the translocation mechanism of the transporter has been established.
Moreover, the peculiar two metal-binding site feature of ferroportin has been widely investigated through site-directed mutagenesis and fluorescence spectroscopy. The different affinity of the two metal binding sites has been assessed allowing for the reconciliation of numerous conflicting data reported in literature. Based on these novel findings, an innovative metal translocation model for ferroportin has been proposed.
Also, the two ferroxidases ceruloplasmin and hephaestin were investigated. Specifically, different mutants of ceruloplasmin were produced and purified from a heterologous expression system for the first time. The potential of obtaining a high-quality recombinant form of this protein for unlocking in-depth analysis has been demonstrated. Similarly, a protocol has been established for the production and purification of full-length hephaestin, enabling future structural and functional characterization. The potential of this protocol has been tested through functional investigation of two cancer-related variants of this protein.
Finally, the interaction between ferroportin and ceruloplasmin has been demonstrated using the Proximity Ligation Assay, resolving a long-standing question about this system. In vitro trials have been conducted to handle and stabilize this protein complex, enabling its future structural characterization
Behind Our Words: Psychological Paths Underlying the Un/Supportive Stance Toward Immigrants in Social Media
No full textThe present work is aimed at exploring the psychological paths underlying supportive and unsupportive social media stances toward immigrants. This investigation is based on a particular case of supportive communication on immigration promoted on line by a public figure (Morandi, a famous Italian singer). The used methodology integrated methods from data science and psychology, and it was based on a machine learning approach combined with a psycho-lexical analysis of online discussions. Results showed that from the words used by social media commenters can be extracted peculiar psychological processes behind supportive and unsupportive stance toward immigrant hosting. In particular, words were qualitatively grouped by defining the underlying value dimension, cognitive, emotional and also attributional processes for both supportive and unsupportive commenters. Thus this study allowed to find fine grained socio-psychological shades by overcoming the simple polarized online stances detection
The different affinity of the two metal-binding sites of human ferroportin drives outward directionality of transport
No full text: Ferroportin, the only known cellular iron exporter, belongs to the major facilitator superfamily of transporters, which cycle between inward-open, occluded and outward-open conformations to translocate substrates across membranes. Recently reported cryoEM structures of ferroportin identified two metal-binding sites in the central cavity of the protein, with site S1 that includes residues D39 and H43, while site S2 is formed by C326 and H507. Here we have employed fluorescence spectroscopy to evaluate the binding affinity for cobalt of human ferroportin. The results suggest that S2 has a higher affinity for cobalt than S1. Results are discussed in view of available structural data on the outward-open conformation of Fpn and of a novel structural model of the inward-open conformation, obtained with a custom implementation of AlphaFold 2. We propose a mechanism by which the outward flux of iron could be driven by the different affinity of the two sites
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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