1,720,961 research outputs found
NK cells expressing KIR2DL2 inhibitory receptor: effect on HHVs infection control in MS disease
No full textLa sclerosi multipla (SM) è una malattia demielinizzante autoimmune del sistema nervoso centrale (CNS), caratterizzata da demielinizzazione infiammatoria acuta e danno assonale indotti da cellule T reattive alla mielina. Tuttavia, non solo le cellule T, ma anche altri fattori, appartenenti al sistema immunitario, sono coinvolti nell'insorgenza e progressione della malattia. Infatti è stato osservato un ruolo significativo delle cellule Natural Killer (NK) nelle forme recidivanti-remittenti della SM. Le cellule NK giocano un ruolo essenziale nel controllo della trasformazione tumorale così come delle infezioni virali, poiché sono in grado di uccidere le cellule aberranti che presentano una diminuita espressione dell'antigene leucocitario umano (HLA) di classe I, mentre risparmiano le cellule esprimenti HLA-I, il cui riconoscimento avviene da parte dei recettori inibitori KIR, regolatori delle funzioni effettrici delle cellule NK. Studi epidemiologici hanno dimostrato che la predisposizione genetica e l'esposizione ad un agente infettivo risultano essere coinvolti nella patogenesi della SM. In particolare, molti dati suggeriscono il coinvolgimento di infezioni da herpes virus. In studi precedenti, valutando il ruolo delle cellule NK in risposta a infezioni da herpes virus in pazienti affetti da SM, abbiamo riscontrato una correlazione interessante tra un'attivazione difettiva delle cellule NK nei confronti dell'infezione e una sovra-espressione del recettore inibitorio KIR2DL2.
Lo scopo di questo progetto è stato quello di studiare i meccanismi molecolari che differenziano il comportamento delle cellule NK in risposta ad infezioni da herpes virus umani (HHVs) in associazione con l’espressione del recettore KIR2DL2. Per questo motivo, abbiamo analizzato l'espressione e la funzione di KIR2DL2 durante l’infezione da HSV-1, HHV-6A, -6B ed EBV. Abbiamo potuto riscontrare che l'attivazione delle cellule NK risultava incrementata nelle cellule NK KIR2DL2- in co-coltura con cellule infettate con HHVs, mentre le cellule NK KIR2DL2+ non risultavano attivate. Sulla base di questi dati abbiamo studiato le possibili modificazioni molecolari ed epigenetiche coinvolte. In particolare abbiamo identificato variazioni nell’espressione di differenti citochine in cellule NK KIR2DL2+ e KIR2DL2-, che riflettono una minore risposta immunitaria in cellule NK esprimenti il recettore KIR2DL2. Inoltre abbiamo indagato una possibile implicazione dei fattori di trascrizione nel modulare l'espressione del KIR2DL2, analizzando l’mRNA e la proteina di Sp1 in cellule KIR2DL2 positive e negative e valutando l'interazione del promotore del recettore KIR2DL2 con il fattore di trascrizione RUNX1. Si è potuto riscontrare un ruolo significativo di entrambi nell’espressione del
KIR2DL2, in particolare di Sp1 nella regolazione e di RUNX1 nella sovra-stimolazione dell’espressione del recettore. In seguito ci siamo occupati di investigare il ruolo delle modificazioni epigenetiche, in particolare della metilazione, nel modulare l'espressione del KIR2DL2 in pazienti con SM. Sulla base dei risultati ottenuti abbiamo ipotizzato che La metilazione del promotore del KIR2DL2 in pazienti con SM, che porta al silenziamento del gene, sembra correlare con una migliore prognosi di malattia. Complessivamente questi dati forniscono un nuovo punto di vista nello studio della risposta immunitaria verso infezioni da herpes virus in pazienti affetti da SM. In particolare, sarà possibile sfruttare l'espressione del recettore KIR2DL2 come target per la modulazione dell'attivazione delle cellule NK.Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS), characterized by acute focal inflammatory demyelination and axonal damage induced by myelin-reactive T cells. However, not only T cells, but also other cell types of the immune system, are involved in the onset and progress of the disease. In fact, it has been proposed a role for Natural Killer (NK) cells in the relapsing-remitting progression of MS. NK cells play an essential role in controlling tumor transformation and viral infection by killing aberrant cells that down-modulates human leukocyte antigen (HLA) class I surface expression, while sparing cells with HLA-I via recognition by killer-cell inhibitory receptors (KIR) that finely tune NK cell effector functions. Epidemiological studies have shown that the genetic predisposition and the exposure to an infectious agent might be involved in MS pathogenesis. In particular, several data suggest the involvement of herpes viruses’ infection.
In previous studies we have evaluated the role of NK cells towards herpes viruses (HHVs) infection in MS patients and we have observed an interesting correlation between a defective activation of NK cells towards infection and an up-modulation of KIR2DL2 inhibitory receptor expression.
The aim of this project was to investigate the molecular mechanisms that differentiate NK cell behavior towards HHVs infection in association with KIR2DL2 expression and the possible implication n MS follow-up. We have analyzed the expression and effect on NK cell activation of KIR2DL2 receptor during HSV-1, HHV-6A, -6B and EBV infection. We have observed an increased activation of NK without KIR2DL2 expression in the presence of HHVs infected cells, whereas KIR2DL2+ NK cells were not able to activate. On the basis of these data, we have investigated the possible molecular and epigenetic modifications involved in the expression of KIR2DL2 receptor during HHVs infections. In particular, we have identified a different cytokine expression profile betweenKIR2DL2 positive and negative NK cells, reflecting a lower activation in KIR2DL2+ NK cells. Moreover, we have investigated a possible implication of transcription factors expression in modulating KIR2DL2 expression. We have analyzed Sp1 mRNA and protein expression in KIR2DL2 positive and negative NK cells cells and evaluated KIR2DL2 promoter interaction with transcription factor RUNX1. We have found a significant role for Sp1 in regulating and for RUNX1 in up-modulating KIR2DL2 expression.
After that, we have investigated the role of epigenetic modification, methylation, in modulating the expression of KIR2DL2 in MS patients. We have observed a correlation between KIR2DL2 promoter methylation, leading to KIR2DL2 gene silencing, and a better MS prognosis.
Altogether these data provide a novel point of view in the landscape of the immune response toward HHVs infection in MS disease, in particular it will be possible to exploit KIR2DL2 receptor expression as a target for modulating NK cell activation
HLA-G molecules in autoimmune diseases and infections
Full text linkHuman leukocyte antigen (HLA)-G molecule, a non-classical HLA-Ib molecule, is less polymorphic when compared to classical HLA class I molecules. HLA-G was first detected on cytotrophoblast cells at the feto-maternal interface but its expression is prevalent during viral infections and several autoimmune diseases. . HLA-G gene is characterized by polymorphisms at the 3' untranslated region and 5’ upstream regulatory region that regulate its expression and are associated with autoimmune diseases and viral infection susceptibility, creating an unbalanced and pathologic environment. This review focuses on the role of HLA-G expression in autoimmune conditions and viral infections
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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