1,720,970 research outputs found
ACE2 up-regulation by MDM2 inhibition counteracts inflammation in human umbelical vein endothelial cells
No full textL'enzima di conversione dell'angiotensina 2 (ACE2) è un recettore presente sulla superficie cellulare coinvolto nel sistema Renina-Angiotensina espresso in diversi tipi di cellule, incluso l'endotelio vascolare. Recentemente, ACE2 ha attirato una notevole attenzione per il suo ruolo come recettore di SARS-CoV-2, l'agente eziologico del virus COVID-19, fornendo un collegamento tra immunità, infiammazione e malattie cardiovascolari. La ridotta espressione di ACE2 è stata identificata in condizioni infiammatorie croniche come diabete, lesioni polmonari, COVID-19 e vasculite. Studi recenti hanno suggerito che MDM2 (Murine Double Minute 2), un noto inibitore di p53, è in grado di regolare i livelli di espressione di ACE2 attraverso l'ubiquitinazione. Per questo motivo, il nostro lavoro mirava a esplorare un potenziale trattamento per ripristinare i livelli di ACE2 e salvare le cellule dall'infiammazione utilizzando nutlin-3a, un inibitore di MDM2, per impedire la degradazione di ACE2 da parte di MDM2. In uno studio preliminare, condotto in un modello dell'epitelio alveolare (A549-hACE2), abbiamo osservato, attraverso la tecnica di western blotting e analisi di immunofluorescenza, un’efficiente sovraregolazione di ACE2 dopo il trattamento con nutlin-3a. Questi dati preliminari ci hanno stimolato a studiare l'effetto di nutlin-3a in modelli di infiammazione basati su cellule endoteliali della vena ombelicale umana (HUVEC). Abbiamo trattato le cellule HUVEC con stimoli infiammatori, TNFα o LPS, per imitare un’infiammazione di tipo acuto. Le cellule sono state sottoposte al trattamento con nutlin-3a a con diverse concentrazioni, i controlli sono stati eseguiti in parallelo con TNF-α, LPS e nutlin-3a usati da soli. Gli effetti biologici mediati da nutlin-3° sono stati studiati a 24 e 48 ore dal trattamento attraverso l’analisi della vitalità cellulare, del ciclo cellulare e dell'apoptosi. Allo stesso tempo, le cellule sono state raccolte per studiare l'analisi dei livelli di espressione della proteina ACE2 e del pathway di p53. Parallelamente, è stato valutato l'impatto sulla proliferazione e la migrazione cellulare mediante saggi in tempo reale xCELLigence. Per valutare lo stato di infiammazione, sono stati raccolti i surnatanti per effettuare l'analisi delle citochine secrete, e inoltre è stata studiata l'adesione dei monociti (Thp-1) alle cellule HUVEC. I risultati hanno mostrato una sovraregolazione concentrazione-dipendente delle proteine ACE2, p53 e MDM2 nelle cellule trattate con nutlin-3a in assenza o presenza di stimoli infiammatori. I risultati evidenziano che il numero di cellule diminuisce significativamente con l'aumentare delle concentrazioni di nutlin-3a da solo e in combinazione con TNF-α o LPS. È stata osservata un'induzione del blocco del ciclo cellulare, accompagnata da bassi livelli di apoptosi, sia in ambienti fisiologici che infiammatori. Inoltre, la nutlina-3a ha mostrato efficacia nel mitigare l'infiammazione riducendo il rilascio di IL-6 nelle cellule esposte a stimoli infiammatori, compromettendo l'adesione dei monociti all'endotelio.
Questi risultati indicano un'efficiente stabilizzazione e controllo dell'infiammazione associata all'inibizione di MDM2, suggerendo che esso rappresenta una molecola efficace come potenziale terapeutico per i disturbi vascolari correlati all'infiammazione.Angiotensin-converting enzyme 2 (ACE2) is a cell surface receptor involved in the Renin-Angiotensin System (RAS) expressed in several cell types, including vascular endothelium. It has recently drawn considerable attention for its role as a SARS-CoV-2 receptor, the causative agent of COVID-19, providing a critical link between immunity, inflammation, and cardiovascular disease. Reduced expression of ACE2 has been identified under chronic inflammatory conditions like diabetes, lung injury, COVID-19, and vasculitis. Recent studies have suggested that Murine Double Minute 2 (MDM2), a well-known p53 inhibitor, regulates ACE2 expression levels through ubiquitination. For this reason, our work aimed to explore a potential treatment to restore ACE2 levels and rescue cells from inflammation by using nutlin-3a, an MDM2 inhibitor, to avoid MDM2-depending degradation of ACE2 protein. In a model of the alveolar epithelium (A549-hACE2), we preliminarily observed an efficient upregulation of ACE2 protein after treatment with nutlin-3a by western blotting and immunofluorescence analysis. These preliminary data stimulated us to study the effect of nutlin-3a in models of inflammation based on Human Umbilical Vein Endothelial Cells (HUVEC). We treated the HUVEC cultures with inflammatory stimuli TNFα or LPS to mimic acute pathologies. Cells were then treated with several concentrations of nutlin-3a, and controls were run in parallel with TNF-α, LPS, and nutlin-3a used alone. After 24h and 48h of treatments, the biological effects mediated by nutlin-3a were studied via cell viability, cell cycle, and apoptosis analysis. At the same time, cells were harvested for p53-gene targets and ACE2 protein expression levels analysis. In parallel, the impact on cellular proliferation and migration was assessed by xCELLigence real-time assays. To evaluate inflammation status, supernatants were collected for secreted cytokines analysis, and monocytes (Thp-1) adhesion to cultures was investigated. Results showed a concentration-dependent upregulation of ACE2, p53, and MDM2 proteins in nutlin-3a treated cells in the absence or the presence of inflammation stimuli. The results highlight that the number of cells decreases significantly with the increasing doses of nutlin-3a alone and combined with TNF-α or LPS. An induction of a cell cycle block was observed, accompanied by low levels of apoptosis, both in physiological and inflammatory environments. Moreover, nutlin-3a mitigates inflammation by reducing the IL-6 release in cells exposed to inflammatory stimuli and impaired monocyte adhesion to endothelium.
These results indicate an efficient ACE2 stabilization and control of inflammation associated with MDM2 inhibition, suggesting an efficient tool with therapeutic potential for vascular disorders related to inflammation
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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