1,720,957 research outputs found
Esplorando la biosintesi di metaboliti specializzati antimicrobici in attinomiceti rari
No full textAntimicrobial resistance (AMR) is reducing antibiotic efficacy faster than new drugs can be developed. This thesis integrates genome-guided discovery of antibiotics with genetic engineering in actinomycetes, moving from scaffold identification to biosynthesis elucidation and strain improvement. Two research lines are presented: (i) discovery of kineomicins, a novel glycopeptide antibiotic (GPA) complex from Actinokineospora auranticolor DSM 44650; and (ii) biosynthesis and production improvement of GE23077, a selective RNA polymerase inhibitor from Actinomadura lepetitiana DSM 109019. Genome mining revealed an atypical GPA biosynthetic gene cluster (BGC) in A. auranticolor, and structural analysis confirmed kineomicins as a new GPA subclass with an unprecedented aglycone. Process optimisation delivered titres above 1 g/L, identifying A. auranticolor as a natural overproducer. For GE23077, a high-quality genome assembly uncovered the gec BGC, encoding a non-canonical NRPS system, tailoring enzymes, transporters, and the regulator gecA. Comparative genomics revealed gec-like clusters in four additional Actinomadura species, which produced GE23077 and new congeners, including a phenyl-substituted analogue. Morphotype selection doubled GE23077 titres, while strain engineering with gecA overexpression or ribosome recycling factor insertion yielded 2- and 4-fold improvements. Overall, this workflow provides novel scaffolds, genetic insights, and enhanced production, advancing antibiotic discovery against AMR.La resistenza agli antibiotici (AMR) riduce l’efficacia degli antibiotici più velocemente di quanto si riesca a sviluppare nuovi farmaci. Questa tesi integra la scoperta genome-guided di antibiotici con l’ingegneria genetica negli attinomiceti, passando dall’identificazione di nuovi scaffold alla chiarificazione della biosintesi e al miglioramento delle produzioni. Il lavoro si concentra su due linee: (i) la scoperta della kineomicina, un nuovo complesso di antibiotici glicopeptidici (GPA) da Actinokineospora auranticolor DSM 44650T; e (ii) la biosintesi e l’aumento della produzione di GE23077, un inibitore selettivo dell’RNA polimerasi da Actinomadura lepetitiana DSM 109019T. Il genome mining ha rivelato un cluster genico biosintetico (BGC) atipico in A. auranticolor, e le analisi strutturali hanno confermato come la kineomicina sia una nuova sottoclasse di GPA, con un aglicone inedito. L’ottimizzazione dei processi ha portato a titoli superiori a 1 g/L, rendendo A. auranticolor un naturale overproduttore. Per lo studio di GE23077, il genoma completo ha permesso di identificare il cluster gec, contenente un sistema NRPS non canonico, enzimi per la sintesi dei precursori, trasportatori e il regolatore gecA. Analisi comparative hanno individuato cluster simili in altre quattro specie di Actinomadura, produttrici di GE23077 e nuovi congeneri, incluso un analogo fenil-sostituito. La selezione morfotipica ha raddoppiato le rese di GE23077, mentre l’ingegneria razionale con la sovraespressione di gecA o l’inserimento del fattore di riciclo ribosomiale ha portato a incrementi rispettivamente di 2 e 4 volte. Nel complesso, questo approccio fornisce nuovi scaffold, conoscenze genetiche e maggiore disponibilità, passi chiave verso nuovi antibiotici contro l’AMR
Unraveling Actinomadura lepetitiana’s color palette: a study on carotenoid production in filamentous actinomycetes
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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