1,720,975 research outputs found

    Lactoferrin against inflammatory and iron disorders in different infection models

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    Lactoferrin (Lf) is a cationic glycoprotein able to chelate two ferric ions per molecule. Human Lf (hLf), a key element of host defenses, is secreted by exocrine glands and by neutrophils. HLf and bovine Lf (bLf), possessing high sequence homology, exert identical functions, such as antimicrobial and antiviral activities. In the last decades, other important Lf activities have been discovered, including the anti-inflammatory one. This Lfs function is strictly dependent by the binding with specific host cell receptors, leading to Lf cell internalization and translocation into the nucleus, thus directly down-regulating pro-inflammatory genes’ expression. In this regard, our group has recently demonstrated the bLf ability in counteracting the tight interplay between inflammatory and iron homeostasis disorders in inflamed macrophages, by down-regulating interleukin (IL)-6 synthesis and rebalancing the expression of main iron-handling proteins, namely ferroportin (Fpn), transferrin receptor 1 (TfR1) and ferritin (Ftn). Here, the role of bLf in different infection models is presented, highlighting its ability to exert a potent action against infection as well as iron and inflammatory disorders. The first model regards a cystic fibrosis (CF) mice suffering from Pseudomonas aeruginosa chronic lung infection. Treatments with aerosolized bLf for 7 days were effective in significantly reducing pulmonary bacterial load. Furthermore, for the first time, we showed that bLf treatment was effective in rebalancing the expression of both iron exporter Fpn and iron storage Ftn, thus reducing pulmonary iron overload. The second model concerns the role of bLf against Chlamydia trachomatis infection in vitro and in vivo. C. trachomatis, an obligate intracellular pathogen causing infections associated to inflammation, requires iron for its replication. In in vitro study bLf interferes with C. trachomatis entry into human epithelial cell line when cell monolayers were pre-treated or treated with the protein at the moment of the infection. Lf exerts a potent anti-inflammatory activity down-regulating IL-6 and IL-8 synthesis as well as rebalancing the expression of Fpn and TfR1 in infected cells. In addition, pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis with a decrease of cervical IL-6 levels. The third and last model regards the in vitro study of bLf antiviral activity against the new coronavirus infection (SARS-CoV-2). The coronavirus infection causes severe acute respiratory syndrome characterized by massive systemic levels of pro-inflammatory cytokines. In in vitro preliminary results, bLf, through its competitive binding with viral component(s) and its interaction with host surface receptors, blocks SARS-CoV-2 entry in different cell models. Interestingly, the in silico results strongly support the hypothesis of a direct recognition between the lactoferrin and the spike S glycoprotein, thus hindering the viral entry into the cells. Moreover, we performed a randomized, prospective, interventional study assessing for 30 days the effect and tolerability of an oral (1 gr/day) and intranasal (about 16 mg/nostril) liposomal lactoferrin on 10 asymptomatic and 22 mild-to-moderate COVID-19 patients. After 15 days of treatment, rRT-PCR revealed a negative conversion of SARS-COV-2 RNA of the naso-oropharingeal swab in 28 patients (87.5%) and in 4 after 30 days. A significant reduction of D-Dimer, IL-6 and ferritin blood levels was observed together with a fast clinical symptoms recovery. No adverse effects were observed

    Sobre la presencia en Galicia de Heterocladium wulfsbergii Hag. y Homalia trichomanoides (Hedw.) B.S.&G. (Musci.)

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    Reinoso, J. & Schumacker, R. Sobre la presencia en Galicia de Heterocladium wulfsbergii Hag. y Homalia trichomanoides (Hedw.) B.S. & G. (Musci). Lazaroa 14:177-178 (1994). En esta nota, reseñamos la presencia en Galicia de los musgos Heterocladium wulfsbergii Hag. y Homalia trichomanoides (Hedw.) B.S. & G que son nuevas citas para las provincias de A Coruña y Lugo respectivamente

    THE STATE OF THE COPPER SITES IN HUMAN CERULOPLASMIN

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    The state of the various, spectroscopically distinguishable copper sites (type 1, type 2, and type 3 copper) of human ceruloplasmin was investigated by electron spin resonance (ESR) spectroscopy. The ESR measurements were performed at 100 K and at X-band during the reaction of the protein with either ascorbate or with ferricyanide. A method was developed to directly measure the contribution of type 1 and type 2 copper signals to the ESR spectrum of the native protein. A signal arising from an unperturbed type 2 copper site, obtained by aerobically treating the protein with ascorbate, allowed the estimation that the number of type 2 copper centers detectable by ESR was substantially lower than unity. A fraction of type 1 copper sites was found to be in the reduced state and could be reoxidized by treatment with ferricyanide. The data obtained were consistent with the presence of three type 1 copper sites per protein molecule. Based on the experimentally determined stoichiometries, computer simulations of the ESR lineshape were carried out which confirmed the presence of three nonequivalent type 1 copper sites and of a noninteger amount of ESR-detectable type 2 copper in human ceruloplasmin

    Novel findings on the copper catalysed oxidation of cysteine

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    The oxidation of cysteine (RSH) has been studied by using O-2, ferricytochrome c (Cyt c) and nitro blue tetrazolium (NET) as electron accepters. The addition of 200 mu M Cu-II to a solution of 2 mM cysteine, pH 7.4, produces an absorbance with a peak at 260 nm and a shoulder at 300 nm. Generation of a cuprous bis-cysteine complex (RS-CuI-SR) is responsible for this absorbance. In the absence of O-2 the absorbance is stable for long time while in the presence of air it vanishes slowly only when the cysteine excess is consumed. The neocuproine assay and the EPR analysis show that the metal remains reduced in the course of the oxidation of cysteine returning to the oxidised form at the end of reaction when all RSH has been oxidised to RSSR. Addition of Cu-II enhances the reduction rate of Cyt c and of NET by cysteine also under anaerobiosis indicating the occurrence of a direct reduction of the acceptor by the complex. It is concluded that the cuprous bis-cysteine complex (RS-CuI-SR) is the catalytic species involved in the oxidation of cysteine. The novel finding of the stability of the complex together with the metal remaining in the reduced form during the oxidation suggest sulfur as the electron donor in the place of the metal ion

    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

    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
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