1,720,953 research outputs found
ALTERAZIONI DELLA BARRIERA EPITELIALE INTESTINALE NELLA MALATTIA DI PARKINSON: RUOLO DEL RECETTORE LRRK2
No full textLa malattia di Parkinson (MP) è una patologia neurodegenerativa multifattoriale caratterizzata da disfunzioni del tratto gastrointestinale (GI) già nelle fasi precoci della malattia. Studi recenti sostengono che l’insorgenza della MP sia riconducibile ad alterazioni che originano nell’apparato digerente, per poi diffondersi progressivamente a livello centrale, attraverso determinate vie nervose e immunitarie che collegano l’intestino al cervello. Negli ultimi anni è stato dimostrato che l’accumulo enterico di α-sinucleina, visibile già nelle fasi prodromiche della malattia, promuove l’attivazione di processi immuno-infiammatori enterici. Tali processi infiammatori contribuiscono alla compromissione dell’integrità della barriera epiteliale intestinale (BEI) con conseguente traslocazione di batteri nocivi dalla mucosa intestinale al compartimento interno, generando, così, un circolo vizioso che contribuisce sia alla cronicizzazione dei processi infiammatori intestinali che allo sviluppo di disfunzioni enteriche tipiche dei pazienti affetti da MP. In tale contesto, recenti studi hanno dimostrato che le cellule gliali enteriche (EGCs), componente fondamentale del Sistema Nervoso Enterico, sono regolatori fondamentali dei processi infiammatori enterici, facendo supporre un loro coinvolgimento nella patogenesi delle disfunzioni GI associate alle fasi iniziali della MP. In particolare, le ultime ricerche scientifiche si sono concentrate nel comprendere il ruolo del recettore Leucine-rich repeat kinase 2 (LRRK2), espresso sia a livello enterogliale che a livello epiteliale, nella patogenesi della MP. Tale recettore, le cui mutazioni sono la causa più frequente di MP ereditaria, è coinvolto in molte vie di segnalazione immuno-infiammatorie ed in condizioni patologiche si attiva esasperando la risposta immuno-infiammatoria con conseguente danno all’organismo. Sulla base di queste considerazioni, la presente tesi ha avuto come obiettivo quello di investigare il ruolo delle EGCs nell’alterazione della BEI nella MP, utilizzando sia un modello murino transgenico A53T che un modello di co-coltura cellulare EGCs/IEC-6 (cellule epiteliali intestinali). In particolare, la ricerca si è focalizzata nel comprendere il ruolo del recettore LRRK2 nel cross-talk tra le EGCs e le IEC-6. Dagli esperimenti in vivo condotti sui topi A53T è emerso che, già nelle fasi prodromiche della malattia è visibile un accumulo di α-sinucleina a livello enterico e un aumento dell’espressione del recettore LRRK2. Inoltre, è stata osservato un aumento del marker gliale enterico (GFAP) e una riduzione dell’espressione della proteina giunzionale (tight junction, TJ) occludina, fondamentale per l’integrità della BEI, nei topi affetti da MP. Al fine di valutare una possibile correlazione tra questi eventi, sono stati condotti esperimenti su co-colture cellulari tra EGCs e IEC-6. Il trattamento con lipopolisaccaride (LPS) e α-sinucleina, utilizzato per mimare in vitro la condizione patologica della MP, ha indotto un incremento nell’espressione dei marcatori gliali GFAP e S100β, suggerendo la presenza di gliosi reattiva. E’ interessante notare, come le cellule gliali attivate hanno mostrato un incremento significativo del recettore LRRK2; tale effetto risulta abolito in presenza dell’antagonista di tale recettore. Come conseguenza dell’attivazione gliale e dell’aumento dell’espressione del recettore LRRK2, è stata osservata una riduzione dell’espressione della TJ nelle IEC-6 trattate con LPS e α-sinucleina. Questi risultati mostrano per la prima volta una correlazione tra attivazione enterogliale, recettore LRRK2 e le alterazioni della BEI in presenza della MP. In particolare, i nostri esperimenti suggeriscono che l’accumulo di α-sinucleina a livello enterico induce attivazione enterogliale e un aumento del recettore LRRK2, con conseguente incremento della permeabilità intestinale nella MP.
In conclusione, questi eventi fisiopatologici rappresentano uno dei primi segni della MP che potrebbero contribuire alle alterazioni intestinali tipiche dei pazienti con MP, e attraverso l’asse intestino-cervello, alla neurodegenerazione e neuroinfiammazione centrale
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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