1,720,978 research outputs found
SARS-CoV-2 INFECTION: EFFECT ON HOST IMMUNE SYSTEM AND ATYPICAL COVID-19 ASSOCIATED-DISEASES
No full textSARS-CoV-2 is a Betacoronavirus and the etiological agent of CoronaVIrus Disease-19 (COVID-19 ). Comparing to MERS and SARS-CoV, SARS-CoV-2 has major pathogenicity, due to its wide tissue tropism. In fact, SARS-CoV-2 infect several tissues due to the large distribution of ACE2 and CD147, the two main receptors used during viral entry phase through interaction with the viral Spike protein. Since SARS-CoV-2 primary transmission route is by respiratory spread of the virus through infected droplets, the typical pathogenesis associated to the virus consists in the pulmonary disease COVID-19, characterized by cytokine storm and ARDS. Thanks to the wide expression of SARS-CoV-2 target receptors, its infection might also develop extrapulmonary diseases and long-COVID-19, impairing gastrointestinal, hepatic, renal, cardiac, placental and neurological systems.
I investigated the mechanisms at the base of typical and atypical SARS-CoV-2 infection, focusing on the modulation of host immune system. In the defense against viral infection, several innate immune effectors are recruited to drive an immune response. This process is triggered by the recognition of “non self” pathogen components, defined as Pathogen Associated Molecular Patterns (PAMPs), by Pattern Recognition Receptors (PRRs ). In particular, viral genome is recognized by intracellular RNA sensors, which include endosomal Toll Like Receptors (TRLs ). I reported the main role of TLR3 and TLR7 receptors in innate anti-SARS-CoV-2 response, which lead to interferon and cytokine production. Another key actor in the recognition of viral infection is represented by Human Leukocyte Antigen (HLA ) molecules, involved in the antigen presentation process. View the HLAs crucial role, their expression is modulated by viruses as an immune escape mechanism. Specifically, I reported that SARS-CoV-2 exploits the expression of non-classical immunomodulatory HLA class I molecules, HLA-G and HLA-E, to avoid host immune system recognition. I investigated the association between HLA-G expression and immune dysfunctions in COVID-19 patients, focusing on neutrophils recruitment, confirming the HLA-G alteration by the virus as the cause of neutrophils infiltration and inflammation. I reported also that NK cell exhaustion in COVID-19 patients seems to involve Spike protein loading on HLA-E of infected cells and its interaction with the inhibitory NKG2A/CD94 receptor on NK cells, suppressing their cytotoxic functions. Another interesting aspect is referred on SARS-CoV-2 vaccination. I confirmed the efficacy of vaccination in inducing both humoral and cell-mediated immunity against virus, sustaining the protection by vaccination. In addition, I analyzed the potential effect of anti-SARS-CoV-2 vaccination in restoring NK cell functions, revealing that one month following the booster dose there was an enrichment in NK activated cells, with memory-like features. Host immune system impairment is also crucial in the onset of COVID-19 extra-pulmonary pathologies. Among these, gastrointestinal COVID-19 is characterized by altered gut functions, and the analysis of COVID-19 bowel biopsies showed a detrimental vascular effect, sustained by elevated VEGF expression levels. This condition involves the engagement of CD147 receptor and HLA-G expression as immune-escape strategies not only referred to bowel pathology, but also impacting pregnancy outcome. In fact, the analysis of placental specimens demonstrated the alteration of those marker in the presence of SARS-CoV-2 infection. Finally, the occurrence of atypical COVID-19 required the administration of therapies even more efficient and specific. Thus, I evaluated the potential employment of synthetic polymeric formulations in counteract SARS-CoV-2 infection. Considering the recent increase in emergent and re-emergent viral infections, this elaborate potentially contributes to the scientific research not only on SARS-CoV-2, but also on other viral infections.SARS-CoV-2 è un Betacoronavirus, e l'agente eziologico del COVID-19 (CoronaVIrus Disease-19). Rispetto ai virus MERS e SARS-CoV, SARS-CoV-2 ha una maggiore patogenicità, dovuta al suo ampio tropismo tissutale. Infatti, SARS-CoV-2 infetta diversi tessuti grazie all’elevata distribuzione di ACE2 e CD147, due dei principali recettori usati durante la fase di ingresso virale attraverso l’interazione con la proteina Spike. Data la principale trasmissione di SARS-CoV-2 attraverso la via respiratoria, la tipica patogenesi associata è la malattia polmonare COVID-19, caratterizzata da casacata citochinica e ARDS (Sindrome da distress respiratorio acuto). Grazie all’ampia diffusione dei recettori bersaglio di SARS-CoV-2, l’infezione può indurre patologie extra-polmonari, definite long-COVID-19, a carico dell’apparato gastrointestinale, epatico, renale, cardiaco, placentare e neurologico. In questa tesi ho analizzato i meccanismi alla base delle infezioni tipiche e atipiche da SARS-CoV-2, concentrandomi sulla modulazione del sistema immunitario dell’ospite. In presenza di un’infezione virale, la prima risposta immunitaria è costituita dal reclutamento di diversi effettori innati. Questo processo è attivato dal riconoscimento di componenti “non-self” del patogeno, i Pathogen Associated Molecular Patterns (PAMPs), da parte dei Pattern Recognition Receptors (PRRs). In particolare, il genoma virale è riconosciuto da sensori di RNA intracellulari, tra cui i Toll Like Receptors (TLRs) endosomiali. La mia ricerca si è concentrata sul ruolo di TLR3 e TLR7 nella risposta innata contro SARS-CoV-2. Altri componenti chiave nel riconoscimento dell’infezione sono le molecole Human Leukocyte Antigen (HLA), coinvolte nella presentazione dell’antigene. Dato il loro ruolo cruciale, la loro espressione è modulata dai virus come meccanismo di evasione immunitaria. Ho dimostrato che SARS-CoV-2 sfrutta l’espressione delle molecole HLA di classe I non-classiche, HLA-G e HLA-E, per eludere il riconoscimento dal sistema immunitario. Ho valutato l’associazione tra l’espressione di HLA-G e le disfunzioni immunitarie nei pazienti COVID-19, specialmente il reclutamento dei neutrofili, confermandone il ruolo nell’induzione di infiltrazione neutrofila ed infiammazione. Inoltre, ho dimostrato che l’anergia delle cellule NK dei pazienti COVID-19 sembra coinvolgere il caricamento della proteina Spike sulla molecola HLA-E espressa dalle cellule infette, e la sua interazione con il recettore inibitorio NKG2A/CD94 delle cellule NK. Ho valutato l’efficacia della vaccinazione anti-SARS-CoV-2 nell’indurre sia l’immunità umorale che cellulo-mediata, confermando la protezione vaccinale. Inoltre, ho valutato l’effetto della vaccinazione anti-SARS-CoV-2 nel ripristinare le funzioni delle cellule NK, dimostrando un incremento delle cellule NK attivate e con funzioni di memoria un mese dopo la dose booster. L’alterazione del sistema immunitario dell’ospite è cruciale anche nel COVID-19 extra-polmonare. Tra queste, il COVID-19 gastrointestinale è caratterizzato da alterazioni funzionali, e le analisi condotte su biopsie intestinali COVID-19 hanno mostrato danni vascolari, sostenuti dall’alta espressione di VEGF. Questa condizione coinvolge l’espressione del recettore CD147 e di HLA-G come strategia di immuno-evasione, osservato anche in gravidanza COVID-19-associata. Infatti, le analisi di tessuti placentari sostengono l’alterazione di tali molecole, in presenza dell’infezione da SARS-CoV-2. L’occorrenza del COVID-19 atipico richiede strategie antivirali più efficienti e specifiche. Perciò, ho valutato il potenziale utilizzo di formulazione polimeriche sintetiche nel contrastare l’infezione da SARS-CoV-2. Considerando il recente aumento di infezioni virali emergenti e riemergenti, questo elaborato contribuisce potenzialmente alla ricerca scientifica non solo riguardo SARS-CoV-2, ma anche su altre infezioni viral
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
Innate Immune Response in SARS-CoV-2 Infection
No full textAn efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
