1,720,968 research outputs found
Ceftaroline in vitro activity against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococci: a short report from Italy
No full textBlaB-15, a new BlaB metallo-β-lactamase variant found in an Elizabethkingia miricola clinical isolate
Full text linkA multidrug-resistant strain of Elizabethkingia miricola was isolated from the urine of a 2-year-old boy hospitalized for severe clinical conditions. The strain produces 2 metallo-β-lactamases belonging to subclasses B1 and B3: a new BlaB variant (BlaB-15) and a GOB-7–like enzyme
Structure based drug design: the discovery of novel inhibitors active against New Delhi Metallo-β-lactamase-1
No full textBackground. The emergence of bacterial strains resistant to available antibiotic armamentarium is nowadays a pressing issue in clinical therapy. Among the several mechanisms of bacterial resistance, the rapid evolution and spread of carbapenemases, β-lactamases (BLs) with versatile hydrolytic capacities able to inactivate last resort carbapenems, represents a menace in treating highly resistant infections. [1-3]
Carbapenem-resistant Enterobacteriaceae (CREs), reported with increased frequency, are progressively spreading throughout the World thus leaving no effective antibiotics. [1-3] In particular CREs overexpressing Metallo beta-lactamases (MBLs; i.e. NDM-1, VIM-2, IMP-1) are high-priority target pathogens for the development of novel antibacterials.
Our studies focused on NDM-1: its substrate promiscuity, its resistance to available drugs, the easiness of variants appearance and transferability make NDM-1 one of the most worrisome BLs. [2] Moreover, respect to serine β-lactamases, no inhibitors for any MBLs are currently available in therapy.
Materials/methods. Looking for new potential MBLs inhibitors we performed a structure-based in silico screening of commercially available library using FLAP, and identified several non β-lactam derivatives as promising candidates active against our target New Delhi metallo-beta-lactamase-1 NDM-1. Candidates were validated in vitro and investigated for their mechanism of inhibition.
Results. The binding affinities of the highest scoring hits revealed, for several of them, micromolar inhibitory activity towards NDM-1. Among molecules selected for targeting NDM-1 few demonstrated an activity comparable to that provided by known inhibitors (Ki for the best-selected inhibitor equal to 0.72 μM; ). The identified inhibitors all share common non-covalent, competitive inhibition mechanism vs NDM-1.
Conclusion. For the best ones, studies for improving their affinity and to investigate their potential to synergize beta-lactam antibiotics are ongoing. X-ray crystallography studies are now in progress to confirm our docking prediction and to deeply investigate the structural requirement necessary for proficuous hit to lead generation.
Figure 1
References
[1] Jean-Marie Frère, Eric Sauvage and Frédéric Kerff. “From “An enzyme able to destroy penicillin » to carbapenemases: 70 years of beta-lactamase misbehavior” Current Drug Targets, (2016). Volume 16. (E-pub ahead of print).
[2] Robert A. Bonomo. “New Delhi Metallo-β-Lactamase and Multidrug Resistance: A Global SOS?”Clin Infect Dis. (2011) 52 (4): 485-487
[3] Donatella Tondi, Alberto Venturelli, Richard Bonnet, Cecilia Pozzi, Brian K Shoichet and Maria Paola Costi. “Targeting Serine Beta lactamases with a novel broad spectrum boronic acid”. Journal Medicinal Chemistry. (2014
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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