1,720,960 research outputs found
MicroRNAs: from biogenesis to post-transcriptional regulatory networks
Full text linkThe discovery of microRNA-based post-transcriptional regulation of gene expression added a novel level of genetic regulation to a wide range of biological processes. Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic and multifactorial disorders and of most human cancers. To bypass limitations of computational predictions of miRNA–target relationships, we developed a method for integrated analysis of miRNA and gene expression profiles in combination with target prediction, allowing the identification and study of post-transcriptional regulatory networks in specific biological contexts. This methodology was also implemented in a web tool, MAGIA, that allows integrating target predictions and miRNA and gene expression profiles for the miRNA–mRNA bipartite networks reconstruction, gene functional enrichment and pathway annotations for results browsing. Network analysis has been applied to highlight the importance of some regulatory elements in the regulatory network reconstructed calculating the drop of network efficiency caused by node deactivation. Biologically relevant results, obtained by bioinfomatic analyses in the frame of different projects, were the starting point for further experimental studies, which identified key miRNA-target relations in cancerogenesis. miRNAs biogenesis is not still completely understood. Thus with the integration of genomic information with sequence and expression data we studied the strand selection bias and the expression behavior of intragenic miRNAs and host genes. In contrast with classical biogenesis model, these analyses highlighted that 5’ and 3’ miRNA strands, the “major” and the “minor” forms, deriving from the same hairpin precursor may co-coordinately contribute to silencing of different sets of target genes. Indeed, the behaved tendency to co-expression of intragenic miRNAs and their “host” mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. In the last year, short RNAs massive sequencing was exploited for a miRNOme analysis of myeloproliferative neoplasms (MPN). This analysis allowed the characterization of short RNAs (known and novel miRNAs, isomiRs and moRNAs) expressed by SET2 cells, a JAK2-mutated cell line model for MPN. moRNAs (microRNA-offset RNA) derived from extended hairpin stem sequences, probably by alternative nuclear and/or cytoplasmic processing. They seem to be conserved across species and the conservation extent correlates with expression level. This evidence suggests that moRNAs might be miRNA co-products, representing a distinct functional class of miRNA-related agents. In conclusion, our analyses were addressed to shed light on the complexity of microRNA-mediated gene regulation, pointing out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities in physiology and in different disease.La scoperta della regolazione post-trascrizionale dei miRNA ha aggiunto un nuovo livello alla regolazione genetica in numerosi processi biologici. Alterazioni nell’espressione dei miRNA possono giocare un importante ruolo nell’insorgenza di svariate patologie ed in particolare in molte neoplasie. Per ovviare alle limitazioni presenti nelle relazioni miRNA-mRNA degli algoritmi di predizione computazionali, è stata sviluppata una metodologia per l’integrazione dei profili d’espressione di miRNA e mRNA con le predizioni dei bersagli biologici dei miRNA, che ha permesso l’identificazione di reti regolative post-trascrizionali in diversi contesti biologici. Questa metodologia è stata inoltre implementata in un “web-tool”, soprannominato MAGIA. Per evidenziare l’importanza di alcuni elementi regolativi presenti nei circuiti biologici è stata applicata la teoria delle reti per l’identificazione di geni critici attraverso la loro de-attivazione nella rete. I frutti di queste analisi bioinformatiche, svolte nell’ambito di numerosi progetti, hanno rappresentato il punto di partenza per successivi studi sperimentali che hanno portato alla scoperta di rilevanti relazioni miRNA-target in specifici tumori. La biogenesi dei miRNA non è stata ancora completamente chiarita, perciò, integrando informazioni derivanti dalle sequenze genomiche e da dati d’espressione, sono stati approfonditi alcuni loro aspetti, quali la teoria di generazione dei miRNA maturi per selezione del filamento e la co-espressione dei miRNA intragenici e dei loro geni ospiti. Le suddette analisi hanno evidenziato che i miRNA generati dal 5’ ed il 3’, derivanti dallo stesso miRNA precursore, supportano solo parzialmente il modello classico della biogenesi dei miRNA, secondo il quale uno dei due miRNA maturi è scelto in modo deterministico e degradato. Entrambe le forme “major” e “minor”, infatti, possono contribuire insieme al silenziamento di gruppi diversi di geni bersaglio. La tendenza alla co-espressione tra i miRNA intragenici e i loro geni ospiti, inoltre, è stata confutata dall’analisi dei loro profili d’espressione, dimostrando che i profili d’espressione dei geni ospite non possono essere usati come stimatori dell’espressione dei miRNA per l’inferenza di reti regolative post-trascrizionali. Nell’ultimo anno, il sequenziamento massivo di brevi RNA è stato sfruttato per l’analisi approfondita di miRNA nelle neoplasie mieloproliferative. Attraverso questo approccio è stato possibile scoprire e caratterizzare numerosi brevi RNA, quali miRNA noti e nuovi, isomiRNA e i moRNA, che sono espressi nelle cellule SET2, linee cellulari con mutazione del gene JAK2. I moRNA (microRNA-offset RNA) derivano dalle sequenze dei precursori dei miRNA, probabilmente da un processo alternativo del nucleo e/o citoplasmatico, e sembrano essere conservati in varie specie. Il loro grado di conservazione è correlato con i livelli d’espressione e si potrebbe dedurre che siano prodotti insieme ai miRNA, ma rappresentando una classe funzionale distinta da essi. In conclusione, le nostre analisi sono state indirizzate a far luce sulla complessità della regolazione dei geni da parte dei miRNA, in particolare sull’importanza delle fasi post-trascrizionali della biogenesi dei miRNA ed il loro ruolo nella regolazione delle attività cellulari fisiologiche ed in diverse patologie
microRNA-offset RNAs (moRNAs): by-product spectators or functional players?
No full textRecent studies have exponentially increased the number of known noncoding RNA categories, including microRNA (miRNA), small interfering RNA (siRNA), PIWI element-interacting RNA and various classes of long noncoding RNA (ncRNA), that fulfill key roles as transcriptional and post-transcriptional regulators and guides of chromatin-modifying complexes [1]. Among these short RNAs, miRNAs are post-transcriptional regulators of gene expression in a wide range of biological processes and diseases [2]. miRNAs are considered as prominent tumour markers, relevant targets for therapy and therapeutic agents [3]. Here, we discuss the discovery of a novel type of miRNA-related small RNA, miRNA–offset RNA (moRNA), whose function is currently unknown
MAGIA, a web-based tool for MiRNA and Genes Integrated Analysis.
Full text linkMAGIA (miRNA and genes integrated analysis) is a novel web tool for the integrative analysis of target predictions, miRNA and gene expression data. MAGIA is divided into two parts: the query section allows the user to retrieve and browse updated miRNA target predictions computed with a number of different algorithms (PITA, miRanda and Target Scan) and Boolean combinations thereof. The analysis section comprises a multistep procedure for (i) direct integration through different functional measures (parametric and non-parametric correlation indexes, a variational Bayesian model, mutual information and a meta-analysis approach based on P-value combination) of mRNA and miRNA expression data, (ii) construction of bipartite regulatory network of the best miRNA and mRNA putative interactions and (iii) retrieval of information available in several public databases of genes, miRNAs and diseases and via scientific literature text-mining. MAGIA is freely available for Academic users a
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
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