1,720,954 research outputs found
Repurposing MK-8245 as a Quorum Sensing Inhibitor to Suppress Virulence and Potentiate Antibiotic Activity in Pseudomonas aeruginosa
Full text linkBackground/Objectives: The rise in multidrug-resistant pathogens such as Pseudomonas aeruginosa (PA), coupled with declining antibiotic development, underscores the need for innovative therapeutic strategies. Repurposing approved drugs provides advantages of safety and rapid development. Since quorum sensing (QS) controls key virulence traits in PA, targeting this pathway represents a promising antivirulence approach. This study aimed to identify and repurpose existing drugs as QS inhibitors. Methods: An in silico docking screen of 3000 FDA-approved or clinically tested compounds was performed against the C4-HSL receptor RhlR. Seventeen candidates were tested in the laboratory strain PAO1 for lactone-dependent signaling inhibition. The most active compound, MK-8245, was further evaluated for effects on growth, cytotoxicity, lactone release, biofilm formation, pyocyanin, elastase, rhamnolipids, and swarming motility. Its activity was also assessed in 20 clinical PA isolates. Results: MK-8245 (40 μM) reduced QS-regulated gene expression by ~60% without affecting viability. In PAO1, it inhibited rhamnolipids (60%), pyocyanin (40%), elastase (25%), biofilm formation, and swarming motility (25%). MK-8245 also enhanced the efficacy of imipenem against biofilms. In clinical isolates, it consistently decreased lactone release (~60%), pyocyanin (~50%), rhamnolipids (~40%), biofilm formation (~30%), and swarming motility (~25%). Conclusions: MK-8245 emerges as a promising antivirulence candidate against P. aeruginosa. By disrupting QS signaling and impairing multiple virulence factors, it attenuates pathogenicity without bactericidal pressure. Its synergy with standard antibiotics and consistent activity in clinical isolates highlight its translational potential and warrant further preclinical evaluation
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
Herpes Simplex virus type 1 infection induces in neuronal cell lines an Alzheimer-like phenotype through inflammasome activation.
No full textreservedLa malattia di Alzheimer (AD) è una condizione neurodegenerativa che provoca un deterioramento delle funzioni cognitive, con un'eziologia non completamente compresa e mancanza di terapie efficaci. L'infezione da Herpes Simplex Virus di tipo 1 (HSV-1) è considerata un possibile fattore scatenante dell'AD: il DNA virale è rilevato nel cervello di pazienti affetti, co-localizzato con placche di β-amiloide. L'infezione persistente di HSV-1 nei neuroni potrebbe causare un'infiammazione cronica, contribuendo alla disfunzione neuronale e alla neurodegenerazione. In questo contesto, l'inflammasoma emerge come un elemento cruciale, coinvolto sia nella risposta alle infezioni che nella neurodegenerazione.
In questo studio abbiamo verificato, in modelli in vivo e in vitro, che l'infezione con HSV-1 e HSV-MUT (mutante che esprime solo alcuni geni immediati-precoci) induce un fenotipo AD-like nelle cellule neuronali. L'infezione con HSV-MUT ha attivato gli inflammasomi NLRP3 e IFI16, aumentando la produzione di caspasi 1 matura e interleuchina-1β. L'inibizione dell'attività enzimatica della caspasi 1 nelle cellule infette ha ridotto l'accumulo di marcatori di neurodegenerazione. Questi risultati evidenziano l'importanza della via inflammasomica nella neurodegenerazione dovuta all'infezione da HSV-1, e sottolineano il ruolo dei geni immediati-precoci. Questa ricerca fornisce un punto di partenza per approfondire la comprensione del meccanismo alla base dell'ipotesi infettiva nell'AD e sviluppare nuove terapie.Alzheimer's disease (AD) is a neurodegenerative condition that causes deterioration of cognitive functions, with an incompletely understood etiology and lack of effective therapies. Herpes Simplex Virus type 1 (HSV-1) infection is considered a possible trigger of AD: viral DNA is detected in the brain of affected patients, co-localized with β-amyloid plaques. Persistent HSV-1 infection in neurons could cause chronic inflammation, contributing to neuronal dysfunction and neurodegeneration. In this context, the inflammasome emerges as a crucial element, involved in both the response to infections and neurodegeneration.
In this study we verified, in in vivo and in vitro models, that infection with HSV-1 and HSV-MUT (mutant that expresses only some immediate-early genes) induces an AD-like phenotype in neuronal cells. Infection with HSV-MUT activated NLRP3 and IFI16 inflammasomes, increasing the production of mature caspase 1 and interleukin-1β. Inhibition of caspase 1 enzymatic activity in infected cells reduced the accumulation of neurodegeneration markers. These findings highlight the importance of the inflammasome pathway in neurodegeneration due to HSV-1 infection, and highlight the role of immediate-early genes. This research provides a starting point to further understand the mechanism underlying the infectious hypothesis in AD and develop new therapies
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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