1,720,984 research outputs found
Microvasculopatia nella sclerosi sistemica: il ruolo del RNA non codificante H19X
No full textBackground: La sclerosi sistemica (SSc) è una patologia autoimmune caratterizzata da infiammazione, vasculopatia e fibrosi della cute e degli organi interni. Gli RNA lunghi non codificanti (lncRNA) sono trascritti non codificanti coinvolti nella regolazione dell'espressione genica. Questo studio è stato mirato caratterizzare la rilevanza funzionale di H19X nella microvasculopatia SSc
Metodi: l'espressione di H19X è stata valutata su dati di sequenziamento dell'RNA a cellula singola (scRNA-seq) su biopsie cutanee di SSc. Sono state eseguire analisi dell'espressione differenziale dei marcatori di danno delle cellule endoteliali (CE) e l'analisi di pathway (KEGG) tra cellule che esprimono e non esprimono H19X. La funzione di H19X è stata studiata nelle CE microvascolare dermica (HDMEC) mediante silenziamento, utilizzando oligonucleotidi antisenso (LNA GapmeRs). L'espressione di H19X è stata analizzata mediante qPCR dopo stimolazione con citochine proinfiammatorie. L'espressione genica è stata misurata mediante qPCR. I livelli di proteine sono stati analizzati mediante Western Blot. L'adesione endoteliale è stata valutata mediante co-coltura di HDMEC e leucociti marcati. La colorazione con falloidina è stata utilizzata per studiare la contrattilità cellulare.
Risultati: i dati si scRNA-seq hanno mostrato una significativa sovraregolazione di H19X nelle CE da SSc rispetto ai controlli sani. Nelle HDMEC, H19X risultava indotto da IFNα, IFNβ e IFNγ. La molecola di adesione VCAM1 è stata identificata come bersaglio, poiché il knockdown H19X ne portava una diminuzione consistente e significativa sia a livello di mRNA che di proteine. Inoltre, anche l'attività di Rac1 e PAK, due effettori VCAM, così come la contrattilità cellulare indotta da VCAM1 sono state ridotte dopo il knockdown di H19X. La correlazione tra molecole di adesione e H19X è stata confermata dall'analisi di co-espressione e dall'analisi di pathway KEGG eseguita sui dati di ScRNA-seq. Una significativa riduzione dell’adesione endotelio – leucocitaria in seguito al silenziamento di H19X è stata dimostrata con studi funzionali
Conclusione: questo studio fornisce evidenza di un ruolo funzionale di lncRNA H19X nella CE microvascolare. Agendo come regolatore delle molecole di adesione, H19X contribuisce in modo significativo alla microvasculopatia associata a SSc.Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, vasculopathy, and fibrosis of the skin and internal organs. Long non-coding RNAs (lncRNAs) are non-coding transcripts involved in the regulation of gene expression. This study aimed to characterize the functional relevance of H19X in SSc microvasculopahty
Methods: H19X expression in SSc skin biopsies was computed on single–cell RNA–sequencing data (scRNA-seq). Analysis of differential expression of endothelial cell (EC) injury markers and pathway enrichment analysis (KEGG) between H19X expressing cells and H19X negative cells was carried out. The function of H19X was investigated in human dermal microvascular EC (HDMEC) by silencing, using locked nucleic acid antisense oligonucleotides (LNA GapmeRs). H19X expression was analyzed by qPCR after HDMEC stimulation with proinflammatory cytokines. Gene expression was measured by qPCR. Protein levels were analyzed by Western Blot. Endothelial adhesion was evaluated by co-culture of HDMEC and fluorescently labelled peripheral blood mononuclear cells (PBMCs). Phalloidin staining was used to study cell contractility.
Results: scRNA-seq data showed a significant upregulation of H19X in SSc compared to healthy EC. In HDMEC, H19X was consistently induced by IFNα, IFNβ and IFNγ. Adhesion molecule VCAM1 was identified as its target, as H19X knockdown lead to a consistent and significant decrease both at mRNA and protein level. Moreover, activity of Rac1 and PAK, two downstream VCAM1 effectors, and VCAM1-induced cell contractility were also reduced following H19X knockdown. Correlation between adhesion molecules and H19X was confirmed by co – expression analysis and KEGG pathway analysis performed on ScRNA-seq data. The functional relevance of H19X on endothelial adhesion was confirmed by PBMCs with H19X silenced HDMEC, where it was demonstrated a significant decrease in leucocyte-to-endothelial cell adhesion.
Conclusion: This study provides evidence for a functional role of lncRNA H19X in microvascular EC. By acting as a regulator of adhesion molecules, H19X contributes significantly to SSc – associated microvasculopathy
Periodic fever syndromes and the autoinflammatory diseases (AIDs)
Full text linkInnate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner a al. first introduced the term "autoinflammation" describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-kappa B-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies.This review aims to provide an overview of the field with the most recent updates (see "Most recent developments in.." paragraphs) and a description of the newly identified AIDs
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
New Insights on Juvenile Psoriatic Arthritis
Full text linkJuvenile psoriatic arthritis (JPsA) is a relatively rare condition in childhood as it represents approximately 5% of the whole Juvenile Idiopathic Arthritis (JIA) population. According to International League of Associations of Rheumatology (ILAR) classification, JPsA is defined by the association of arthritis and psoriasis or, in the absence of typical psoriatic lesions, with at least two of the following: dactylitis, nail pitting, onycholysis or family history of psoriasis in a first-degree relative. However, recent studies have shown that this classification system could conceal more homogeneous subgroups of patients differing by age of onset, clinical characteristics and prognosis. Little is known about genetic factors and pathogenetic mechanisms which distinguish JPsA from other JIA subtypes or from isolated psoriasis without joint involvement, especially in the pediatric population. Specific clinical trials testing the efficacy of biological agents are lacking for JPsA, while in recent years novel therapeutic agents are emerging in adults. In this review, we summarize the clinical features and the current evidence on pathogenesis and therapeutic options for JPsA in order to provide a comprehensive overview on the clinical management of this complex and overlapping entity in childhood
Systemic sclerosis sine scleroderma in children
No full textOBJECTIVE: Juvenile systemic sclerosis (JSSc) is a rare condition in childhood and its variety with no skin involvement, sine scleroderma (ssJSSc), is anecdotal. We report the first case series of patients with ssJSSc. METHODS: Demographic, clinical and laboratory data of patients with JSSc followed at our centre were retrospectively collected. Patients with no skin involvement but with all of the features RP, positive ANA, intestinal dysmotility and/or interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH) and/or cardiac or renal involvement typical of scleroderma were defined as having ssJSSc and compared with those with classic JSSc (cJSSc). RESULTS: Among 52 JSSc patients seen in 20 years, five (9.6%) presented with ssJSSc. Their clinical features and those of the only two patients reported in the literature so far were compared with classic JSSc with available complete data. Six patients had cardiac involvement as presenting feature, three primary cardiomyopathy, three secondary to PAH. Two patients died after a brief disease course and one rapidly underwent heart transplantation. In comparison with cJSSc, ssJSSc showed a significantly longer diagnostic delay (20.1 vs 8.3 months, P = 0.017), higher frequency of cardiac involvement (85.7 vs 15.6%, P = 0.001) and worse outcome, intended as mortality or end-stage organ failure rates (42.9% vs 6.2%, P < 0.001). CONCLUSION: Cardiac involvement represents the most important characteristic of ssJSSc and carries a high morbidity and mortality rate. The longer delay in diagnosis underlines the need for a comprehensive rheumatological work-up in patients with isolated cardiomyopathy or PAH/ILD
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
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