1,721,053 research outputs found
State of the Art in the Development of Human Serum Carnosinase Inhibitors
Full text linkHuman serum carnosinase is an enzyme that operates the preferential hydrolysis of dipeptides with a C-terminus histidine. Only higher primates excrete such an enzyme in serum and cerebrospinal fluid. In humans, the serum hydrolytic rate has high interindividual variability owing to gene polymorphism, although age, gender, diet, and also diseases and surgical interventions can modify serum activity. Human genetic diseases with altered carnosinase activity have been identified and associated with neurological disorders and age-related cognitive decline. On the contrary, low peripheral carnosinase activity has been associated with kidney protection, especially in diabetic nephropathy. Therefore, serum carnosinase is a druggable target for the development of selective inhibitors. However, only one molecule (i.e., carnostatine) has been discovered with the purpose of developing serum carnosinase inhibitors. Bestatin is the only inhibitor reported other than carnostatine, although its activity is not selective towards serum carnosinase. Herein, we present a review of the most critical findings on human serum carnosinase, including enzyme expression, localization and substrate selectivity, along with factors affecting the hydrolytic activity, its implication in human diseases and the properties of known inhibitors of the enzyme
Unexpected reactivity of the antiseptic domiphen bromide
No full textFor nearly ten decades parabens have been employed as preservatives in a broad variety of preparations. Since parabens were detected in breast cancer cells[1] they have been under scrutiny for their putative role in promoting cancerogenesis.
The food, pharmaceutical and cosmetic industries are yearning for alternatives to these benchmark preservatives and “paraben-free” claims have become popular advertising messages. From a technical stand point, parabens are: 1) very versatile species with a reliable antimicrobial efficacy; 2) easy to incorporate; 3) stable over a broad pH range.
Domiphen bromide is an aromatic quaternary ammonium salt employed as antiseptic, antimicrobial and disinfectant. These properties combined with a good workability make domiphen a possible alternative for parabens. Anyhow, the co-presence of bromide as a counterion and aromatic ring highly reactive to electrophilic substitutions suggests that accidental bromide oxidation to bromine can lead to phenyl bromination.
In this study we developed hyphenated analytical strategies combining HPLC, LC/MS and NMR to monitor such reactions. Indeed we found that domiphen bromide undergoes bromination even under mild conditions. In details, mild oxidant conditions at different pH values have been investigated in order to mimic the variability of preparations. HPLC analyses were carried out under conditions suitable for LC/MS, which clearly proved the formation of the bromo derivative. Moreover, NMR analyses indicated that halogenation occurred at the para position
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
Top–down and bottom–up mass spectrometric analysis of covalent modifications of albumin cys34 as biomarker of oxidative stress
No full textAn integrated high resolution mass spectrometric and informatics approach for the rapid identification of flavonoids in plant extract
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A TANDEM MS PRECURSOR-ION SCAN APPROACH FOR THE IDENTIFICATION OF VARIABLE COVALENT MODIFICATION OF ALBUMIN CYS34 TO STUDY VASCULAR CARBONYLATION
No full textTo date, several experimental evidences confirm that protein carbonylation induced by reactive carbonyl species (RCS) is involved in the pathogenesis of atherosclerosis and subsequently in the development of CVD. Hence, an analytical approach aimed to identify and characterize vascular RCS would be an important tool for the following goals: (i) to better understand the pathogenetic role of RCS, (ii) to monitor and predict the progression of the disease, (iii) to identify novel drug target, and (iv) to demonstrate the efficacy of carbonyl sequestering agents. We recently found that human serum albumin (HSA) is a detoxyfing vascular protein of reactive carbonyl species (RCS) through a covalent adduction mechanism, and that Cys34 is the most reactive site, giving the corresponding Michael adduct [1]. Since Cys34 is one of the main vascular targets of RCS, the identification and characterization of the covalent Cys34 modifications would be a powerful tool to study vascular carbonylation and to reach the goal above mentioned.
To do this, we set-up a mass spectrometric approach that permits to identify unknown covalent modifications of Cys34 based on a triple quadrupole mass spectrometer in pre-cursor ion scan mode. In particular, by considering the trypsin/chymotrypsin digested peptide containing Cys34 (LQQCPF), the y and b fragment which precedes and follows the modification site are selected as precursor ions. The data analysis by using an algorithm developed by us, permits a rapid and specific search of the precursor-ions series attributed to native and modified target peptide. In a following step, the identified pre-cursor ions are selected for product ion scan analysis in order to identify and characterize the type of adduction. The method has been validated by using 4-hydroxy-trans-nonenal (HNE) as a RCS model. Human serum was incubated in the presence of HNE (10 nmoles ml-1), then albumin isolated by affinity chromatography and digested by using trypsin/chymotrypsin; the m/z 370.1 (b3) and m/z 263.1 (y2) fragment ions were used as precursor-ions. The approach identified two peaks relative to the LQQCPF native peptide at m/z 792.4 and the corresponding Cys34-HNE adduct at m/z 893.3, as confirmed by MS/MS. In summary the tandem MS approach here reported is a powerful tool for the rapid identification of unknown covalent protein modifications.
References
1. Aldini G. et al.; J. Mass Spectrom., 41, 1149-61 (2006
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
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