1,721,126 research outputs found
Possibile coinvolgimento del misfolding della componente proteica delle LDL nell’aterogenesi
Full text linkNelle fasi precoci dell’aterogenesi, la ritenzione subendoteliale dei droplets lipidici è associata ad una risposta infiammatoria all’insulto, che culmina con la formazione delle “foam cells” e delle placche. Le lipoproteine a bassa densità (LDL) sono le principali costituenti dei droplets subendoteliali. Si ritiene che l’intero processo avvenga a seguito di modificazioni delle LDL. Nella ricerca di LDL modificate nel plasma, sono state identificate le LDL elettronegative (LDL(-)) ritenute associate ai maggiori marker di rischio. L’apoproteina nelle LDL(-) è misfolded; in questo lavoro mostriamo che questa modificazione avvia il processo di aggregazione delle LDL native, in conformità con il tipico pattern di amilodoigenesi proteica. Dopo una fase di latenza, la cui lunghezza dipende dalla concentrazione di LDL(-), il light scattering e la microscopia a forza atomica rivelano una precoce crescita esponenziale degli intermedi globulari, che evolvono in fibrille. Questi intermedi sono simili ai droplets subendoteliali presenti nelle placche ateromatose e differiscono da quelli prodotti da ossidazione o manipolazione biochimica. Durante l’aggregazione, misure di ellitticità e fluorescenza del triptofano mostrano una diffusione a “domino” del misfolding dalle LDL(-) a tutte le LDL. L’analisi computazionale della sequenza primaria dell’apoproteina predice l’esistenza di un dominio instabile, prono all’aggregazione, nella regione 2. Il misfolding dell’apoproteina ben rappresenta una modificazione in grado di trasformare questo carrier del colesterolo nell’iniziatore della risposta all’insulto nella parete arteriosa.
Sebbene le LDL(-) possano essere prodotte in vitro attraverso varie manipolazioni, il meccanismo coinvolto nella loro generazione in vivo rimane oscuro.
Usando un modello fisiologico, abbiamo dimostrato una spontanea e considerevole produzione di LDL(-) incubando il plasma non processato a 37°C. Oltre ad una maggiore frazione di LDL(-) amilodoigeniche, le LDL purificate da plasma incubato contengono un maggior livello di lisofosfolipidi e acidi grassi liberi; l’analisi dell’impacchettamento dei lipidi nelle LDL rileva il loro rilassamento. Dai risultati ottenuti, possiamo affermare che durante l’incubazione del plasma avviene una destabilizzazione dei lipidi e un misfolding proteico, accanto alla generazione di particelle prone all’aggregazione. Tutti questi fenomeni possono essere prevenuti inibendo le fosfolipasi A2 secretorie, calcio-dipendenti. Il nostro modello di incubazione del plasma, senza la rimozione dei prodotti di reazione, mostra effettivamente un’azione reciproca lipidi/proteine nelle LDL, dove la destabilizzazione dei lipidi dopo lipolisi minaccia la struttura dell’apoproteina, che modificata diventa prona all’aggregazione.In early atherogenesis, subendothelial retention of lipidic droplets is associated with an inflammatory response-to-injury, culminating in the formation of foam cells and plaque. Low density lipoprotein (LDL) is the main constituent of subendothelial lipidic droplets. The process is believed to occur following LDL modification. Searching for a modified LDL in plasma, electronegative LDL (LDL(-)) was identified and found to be associated with major risk biomarkers. The apoprotein in LDL(-) is misfolded, and we show here that this modification primes the aggregation of native LDL, conforming to the typical pattern of protein amylodoigenesis. After a lag phase, whose length depends on LDL(-) concentration, light scattering and atomic force microscopy reveal early exponential growth of intermediate globules, which evolve into fibrils. These globules are remarkably similar to subendothelial droplets in atheromatous lesions and different from those produced by oxidation or biochemical manipulation. During aggregation, ellipticity and tryptophan fluorescence measurements reveal a domino-style spread of apoprotein misfolding from LDL(-) to all of the LDL. Computational analysis of the apoprotein primary sequence predicts an unstable, aggregation-prone domain in the regulatory 2 region. Apoprotein misfolding well represents an LDL modification able to transform this cholesterol carrier into a trigger for a response-to-injury in the artery wall.
Although LDL(-) has been produced in vitro through various manipulations, the mechanisms involved in its generation in vivo remain obscure. By using a more physiological model, we demonstrate spontaneous, sustained and noticeable production of LDL(-) during incubation of unprocessed human plasma at 37°C. In addition to a higher fraction of amyloidogenic LDL(-), LDL purified from incubated plasma contains an increased level of lysophospholipids and free fatty acids; analysis of LDL lipids packing reveals their loosening. As a result, during plasma incubation, lipid destabilization and protein misfolding take place, and aggregation-prone particles are generated. All these phenomena can be prevented by inhibiting calcium-dependent secretory phospholipases A2. Our plasma incubation model, without removal of reaction products, effectively shows a lipid-protein interplay in LDL, where lipid destabilization after lipolysis threatens the apoprotein’s structure, which misfolds and becomes aggregation-prone
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
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