1,721,018 research outputs found
HIGH RESOLUTION MASS SPECTROMETRIC STRATEGIES FOR DETECTION OF PROTEINS AND PEPTIDES COVALENTLY MODIFIED BY ELECTROPHILIC XENOBIOTICS AND ENDOGENOUS INTERMEDIATES
Full text linkNon enzymatic protein covalent modifications are involved in the toxic effects induced by electrophilic xenobiotics as well as by endogenous cytotoxic oxidation by-products. Aim of my Ph.D work was to set-up MS methods for the identification, characterization and quantification of non-enzymatic covalently modified proteins and peptides in biological matrices. To reach this goal both tandem MS and high resolution approaches were employed due to the wealth of structural and molecular information that these techniques can provide.
As a first step the MS methods were applied for understanding in both in vitro and ex vivo conditions the mechanism of protein haptenation induced by amoxicillin (AX). The MS approach was then focused to study in ex vivo condition the covalent reaction between histidine dipeptides, such as carnosine, and toxic endogenous intermediates like reactive carbonyl species (RCS).
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
Mass spectrometric strategies for studying albumin covalent modifications induced by xenobiotics and endogenous electrophilic cytotoxic compounds
No full textProtein covalent modification is involved in the toxic mechanisms of electrophilic xenobiotics as well as of endogenous cytotoxic compounds such as reactive carbonyl species generated by oxidative stress. Protein covalent modification is irreversible and unrepairable and besides inducing a loss of protein conformation and of functional integrity, it can make the adducted proteins immunogenic and pro-inflammatory. Identification and characterization of covalent protein adducts represent an important aspect of pharmaceutical analysis, not only to predict idiosyncratic reactions but also to elucidate cytotoxic mechanism at cellular levels and to find novel biomarkers of electrophilic/oxidative stress.
Human serum albumin (HSA) is considered the main blood protein target of circulating electrophilic compounds and this is due not only to its relevant plasma concentration (≈ 0.6 mM) but also because the presence of several accessible nucleophilic sites such as Cys34, Lys199 and 525. For this reason, HSA protein adducts are searched by using different analytical techniques and among these, mass spectrometry has attained a central role because of the wealth of structural and molecular information that can be obtained. MS approach not only reveals the identity of the adducted protein but also clarifies the stoichiometry of reaction, the aminoacid site undergoing biotransformation, the reaction products and hence the mechanism of reaction. Such an approach has been applied in our laboratory to fully elucidate the HSA binding by amoxicillin (AX) and by 4-hydroxy-trans-2-nonenal (HNE) which is an endogenous electrophilic RCS generated by lipid-peroxidation.
The binding of HSA with amoxicillin was investigated since it is considered a key process for the allergic response of the drug. HSA binding by AX was firstly studied by a top-down MS approach and then the identification of the adducted HSA sites was carried out by a novel bottom-up approach based on a precursor ion approach. At the lowest AX concentration, we detected one main AX-HSA adduct involving residues Lys 190, 199 or 541, whereas higher AX concentrations elicited a more extensive modification. These findings provide novel tools and insight for the study of protein haptenation and the mechanisms involved in AX-elicited allergic reactions.
HNE is one of most abundant and toxic lipid-peroxidation derived compound, which reacts with HSA. In a previous study we fully identified the protein adduct in terms of stoichiometry, reaction kinetic and sites of adduction [1]. We now set-up a LC-ESI-MS/MS approach in order to quantitate the protein adduct. The method consists to digest the protein and quantitate the adducted peptides by using a triple quadrupole MS analyzer working in multiple reaction monitoring mode. The isotope dilution technique was used for quantitative analysis and using deuterium labelled HNE adducted peptides. The method was firstly validated and it is now applied to measure HNE-adducted albumin in the sera of patients as a novel biomarker of oxidative stress.
References
1. Aldini G et al.Albumin is the main nucleophilic target of human plasma: a protective role against pro-atherogenic electrophilic reactive carbonyl species? Chem Res Toxicol. 2008,21,824-35
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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