1,720,956 research outputs found
Structural and biochemical characterization of ribosome small subunit-dependent GTPase A (RsgA) from Pseudomonas aeruginosa
Full text linkThe increase in antibiotic resistance among pathogenic bacterial strains presents a significant health threat. The main efforts to combat antibiotic resistance are focused on the development of new antibiotics targeting protein biosynthesis. Ribosome, the large molecular machine responsible for this process, and proteins involved in the translational process represent ideal targets of molecules with antibacterial activity.
The ribosome assembly in vivo is an intricate and finely tuned process promoted by the action of several proteins acting as assembly factors, whose precise role is still largely unknown. Small GTPases represent the largest class of ribosome assembly factors in bacteria and are emerging as possible targets to be explored for the development of novel antibacterial strategies. Among them, of particular interest is the Ribosome small subunit-dependent GTPase A (RsgA).
RsgA is a late-stage ribosome biogenesis factor involved in the 30S subunit maturation, broadly conserved among bacteria but absent in eukaryotes. RsgA is a circulary permutated GTPase that belongs to an interesting class of GTPases, termed HAS-GTPase, that lack the conserved catalytic glutamine. The circularly permutated GTP binding site is flanked by an OB-fold domain at the N-terminus and by a zinc binding domain at the C-terminus. Despite the large amount of biochemical, structural and genetic data on RsgA achieved in the last decade, its mechanism of action is still not completely understood.
Here we focus on the structural and functional characterisation of RsgA from the human pathogenic bacterium Pseudomonas aeruginosa (PaRsgA). The main goal of this work is the determination of the PaRsgA structure by X-ray crystallography. To date, no structure is available for RsgA from this opportunistic pathogen. This knowledge will allow investigate the molecular features for the recognition of GDP and GTP as well as the key determinants for the mechanism of GTP hydrolysis. Moreover, an accurate kinetic analysis of PaRsgA interaction with GDP and GTP, together with a detailed functional characterization of PaRsgA, provided the determination of substrates affinity and biochemical parameters of GTP hydrolysis.
The results obtained will pave the way for future experiments aimed at the characterization of the binding mechanism underlying ribosome recognition and to get key insight the GTPase activity of PaRsgA in the presence of other assembly factors and/or the ribosomal particle
Molecules that target nucleophosmin for cancer treatment: an update
Full text linkNucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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