1,720,964 research outputs found
identificazione e caratterizzazione di una nuova miopatia vacuolare causata da una mutazione nel gene PLIN4 e possibili strategie per lo sviluppo di una terapia
No full textIn una famiglia affetta da miopatia vacuolare distale abbiamo effettuato esoma genoma e RNAseq non riuscendo ad individuare varianti codificanti verosimilmente patogeniche.
Contemporaneamente, una paziente con una ricombinazione si è sottoposta a biopsia muscolare nella quale un’analisi immunistochimica ha mostrato un aumentato segnale a livello subsarcolemmale e all’interno dei vacuoli, di due proteine legate alla degradazione delle proteine misfolded e aggregate, p62/SQSTM1 e le proteine ubiqutinate (FK2).
La stessa analisi su pazienti con severità del fenotipo media o grave, ha mostrato una correlazione con l’intensità di queste marcature.
Pertanto abbiamo ipotizzato che la proteina che veniva marcata in maniera così specifica dovesse essere la nostra proteina mutata. Abbiamo quindi effettuato una microdissezione laser dei vacuoli con analisi di spettrometria di massa, evidenziando così che la proteina accumulata nei vacuoli e codificata dal gene PLIN4 presente sull’aplotipo comune, era perilipina 4.
Dalla rianalisi dei dati di NGS abbiamo individuato un picco di coverage compatibile con una possibile ripetizione della sequenza.
Un sequenziamento long-read usando la tecnologia Oxford Nanopore Technology, ha identificato una espansione di 9x99 nucleotidi nella regione dell’esone 3, codificante per il dominio anfipatico di perilipina-4, regione strutturalmente correlata alle eliche anfipatiche presenti in α-sinucleina e nelle apolipoproteine.
L’analisi immunoistochimica focalizzata sul pathway dell’aggreafgia, ha confermato che l’accumulo di perilipina-4 nel muscolo è associato all’attivazione di questo pathway, mediato dall’ubiquitinazione degli aggregati e deputato all’eliminazione degli stessi tramite autofagia.
Questa nuova patologia è quindi una malattia da accumulo di aggregati, causata da una espansione di una regione della proteina con apparente incapacità dell’aggrefagia stessa di controllarne l’accumulo.
Lo studio del meccanismo molecolare a livello cellulare, non è stato possibile nei mioblasti derivati da biopsie dei pazienti, in quanto questa proteina non risulta essere espressa a questo livello.
Pertanto, abbiamo deciso di generare un modello di overespressione nel quale la proteina mutata e quella wild-type verranno confrontate per validare la propensità della variante mutata a causare precipitazione di aggregati.In a family affected by distal vacuolar myopathy we performed genome exome and RNAseq, failing to identify probably pathogenic coding variants.
At the same time, a patient with a recombination underwent a muscle biopsy in which an immunohistochemical analysis showed an increased signal at the subsarcolemmal level and within the vacuoles, of two proteins linked to the degradation of the misfolded and aggregated proteins, p62 / SQSTM1 and ubiqutinated proteins (FK2).
The same analysis on patients with increasing severity of the phenotype showed a correlation with the intensity of these proteins’ signals.
Therefore, we hypothesized that the protein that was labeled so specifically must be our mutated protein. We then performed a laser microdissection of the vacuoles with mass spectrometry analysis, thus highlighting that the protein accumulated in the vacuoles and encoded by the PLIN4 gene present on the common haplotype, was perilipin 4.
From the re-analysis of the NGS data we identified a coverage peak compatible with a possible repetition of the sequence.
Long-read sequencing using Oxford Nanopore Technology identified an expansion of 9x99 nucleotides in the exon 3 region, encoding the amphipathic domain of perilipin-4, a region structurally related to the amphipathic helices present in α-synuclein and apolipoproteins.
The immunohistochemical analysis focused on the aggreaphagy pathway confirmed that the accumulation of perilipin-4 in the muscle is associated with the activation of this pathway, mediated by the ubiquitination of the aggregates and responsible for eliminating them through autophagy.
This new pathology is therefore an aggregate accumulation disease, caused by an expansion of a region of the protein with the apparent inability of the aggrephagy itself to control its accumulation.
The study of the molecular mechanism at the cellular level was not possible in myoblasts derived from patient biopsies, as this protein does not appear to be expressed at this level.
Therefore, we decided to generate an overexpression model in which the mutated and wild-type proteins will be compared to validate the propensity of the mutated variant to cause aggregate precipitation
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
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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