1,720,976 research outputs found
Interaction between mechanism of attention selection in space and time: Behavioural and electrophysiological evidence
Full text linkI meccanismi attentivi consentono di selezionare dall'ambiente circostante le informazioni utili allosvolgimento di un determinato compito. Negli ultimi trenta anni, i processi coinvolti nella selezionedi informazioni di natura spaziale sono stati ampiamente investigati, mentre rimangono ancora dachiarire i meccanismi coinvolti negli aspetti di selezione temporale. I tre esperimenti riportatiall'interno di questa tesi sono volti ad indagare alcuni degli aspetti legati alla capacità di selezionaregli eventi nel tempo ed in che modo gli aspetti temporali e quelli spaziali interagiscono tra loro.Nel primo esperimento è stato impiegato un compito di Giudizio di Ordine Temporale (TOJ) perinvestigare la relazione esistente tra disturbi di selezione nello spazio e nel tempo in pazienti coneminegligenza spaziale unilaterale. Una forte compromissione dei meccanismi di selezione neltempo è stata rilevata per le coppie di stimoli presentate in porzioni dello spazio in cui il deficitspaziale è più marcato, suggerendo l'esistenza una relazione tra gli aspetti spaziali e quelli temporalinella modulazione del deficit.Nel secondo e nel terzo esperimento è stato investigato l'orientamento dell'attenzione nel tempoutilizzando stimoli che, grazie ad un movimento con velocità regolare o irregolare, rendonopossibile il generarsi di aspettative temporali e di verificare cosa avviene quando tali aspettativevengono disattese. La regolarità del movimento si è rivelato essere un indice importante nelgenerare aspettative temporali che a loro volta influenzano profondamente la performancediminuendo sensibilmente la velocità di risposta del soggetto. Inoltre, la registrazione dei potenzialievocati ha evidenziato come aspettative spaziali e temporali interagiscano influenzando l'analisidello stimolo fin dalle prime fasi di elaborazione.The study of mechanisms involved in spatial attention is one of the most investigated field inmodern neuroscience, but in the last years a growing interest has been devoted to unveil themechanisms concerning also the temporal aspects of attention. In this thesis three experiment arereported that tried to cast more light on the temporal aspects of attention and on the relationshipbetween spatial and temporal attentional mechanisms.In the first experiment the relationship between spatial and temporal deficit in selective visualattention has been investigated in a group of neglect patients using a temporal order judgement task(TOJ). The main finding is a stronger impairment in temporal selection for spatial position in whichthe attention selection is more impaired, suggesting an interaction between the two aspects in themodulation of the deficit.The second and the third experiment investigated temporal expectations generated by a regularrhythm. In particular, the impact of exogenous and endogenous temporal expectation has beencompared in a discrimination task, revealing the pervasive effect of regularity of movement andspeed in orienting attention in time. Moreover, it has been confirmed the combined effect of spatialand temporal expectations in modulation of electrophysiological response.These results suggest the existence of an interaction between spatial and temporal mechanisms ofattention
A SVM-based method to classify RBM20 affected and not affected exons
Full text linkMutations of RNA binding motif protein 20 (RBM20) have been recently reported to cause Human dilated cardiomyopathy (DCM) (Brauch et al., 2009, Li et al., 2010). DCM is the major cause of heart failure and mortality around the world (Jefferies and Towbin, 2010). Overall, 25–50% of DCM cases are familiar and causative mutations which have been described in more than 50 genes encoding mostly for structural components of cardiomyocytes. RBM20 belongs to the family of the SR and SR-related RNA binding proteins which assemble in the spliceosome taking part in the splicing of pre-mRNA. RBM20 is mainly expressed in striated muscle, with the highest levels in the heart (Guo et al., 2012). Due to its involvement in DCM, RBM20 was studied a lot to unveil its mechanism of action and its RNA targets (Guo et al., 2012, Li et al., 2013). Guo and colleagues reported a set of 31 genes showing a RBM20 dependent splicing from a whole transcriptome analysis in rats and humans (Guo et al., 2012). More recently, Maatz and colleagues reported an additional set of 18 rat genes and observed that RNA sequences recognized by RBM20 are likely to be located in the 400 nucleotides flanking the exons whose alternative splicing is regulated by RBM20 (Maatz et al., 2014). However, both the suggested RNA sequence which is recognized by RBM20 and its over-representation over the flanking regions of affected exons remain poor predictors to target genes presenting splicing events regulated by RBM20. The aim of this work was, thus, to characterize, through a bioinformatic approach, the sequence motifs of the exons whose alternative splicing was affected by RBM20, in order to ameliorate the prediction of the genes (exons) affected by RBM20. A differential expression analysis was performed to select the dataset of RBM20 affected exons; a further dataset was retrieved from literature data (Maatz et al., 2014). A Support Vector Machine (SVM) approach evaluating more kinds of genetic elements binding in the flanking regions of our target exons was used. A SVM method was chose to classify RBM20 affected and not affected exons, but other machine learning algorithms could have been used as well; however, SVM is among the most commonly used ones. From the analyses, our model resulted to well discriminate RBM20 affected from not affected exons. From a biological and functional point of view, this approach helps us to target novel candidate genes associated to diseases depending on a dysregulation of RBM20. This study provided additional information about RBM20 regulation of target exons, based not only on the RNA binding site, but also on other genetic elements associated to the binding site. Furthermore, we proposed the first model based on a SVM algorithm for the classification of RBM20 affected and not affected exons
A study to find sequence motifs that affect splicing of exons regulated by RBM20
No full textRecent studies showed that RNA binding motif protein 20 (RBM20) is involved in the regulation of the alternative splicing of sevaral genes both in rats and humans. RBM20 affects the expression level of the target genes, through activation (rarely) or repression (more often) of the regulated exons. Mutations in RBM20 have been shown to cause human dilated cardiomyopathy, a major source of mortality in the developed world. RBM20 RNA-binding site maps in the intronic sequence of the target genes in close proximity to differentially spliced exons and a significant overrepresentation of RBM20 binding sites in these regions was noticed. Nevertheless, a rule based on the number and the location of the sites flanking RBM20 regulated exons, and other possible still unknown sequence features, that allow to characterize an exon as regulated by RBM20, has not been found yet.
The aim of this study is to find genes, especially exons, whose alternative splicing is affected by RBM20, through a differential analysis of existing RNA sequencing data of human and rat cardiomyocytes in two different conditions: presence and absence of RBM20. Then, we aim to define in greater detail the characteristics of the regions flanking RBM20 regulated exons.
RNA sequencing data of human and rat cardiomyocytes used by Guo et al. were downloaded and used. Rat samples presented three different conditions: 3 wild type (RBM20+/+), 3 heterozygosity (RBM20+/-) and 3 deletion (RBM20-/-) samples. Human samples were in the two different conditions: 2 control individuals (RBM20+/+) and an individual with mutated RBM20 (RBM20-/-). Rat reads were mapped against the reference rat genome RGSC3.4, human reads were mapped against the reference human genome GRCh37. I used DEXSeq program, locally installed, to perform the exons differential analysis.
The differential analysis between RBM20+/+ and RBM20-/- rat samples found 96 differentially expressed exons (p. adj 1). The differential analysis between RBM20+/+ and RBM20-/- human samples found 1816 differentially expressed exons (p. adj 1). Only 8 genes differentially expressed were found common between the two species.
After having produced the catalogue of human and rat exons affected by RBM20, we are now proceeding by evaluating if there are sequence differences in the regions flanking the exons affected by RBM20 to identify the characteristics (eg. the density of sites recognized by RBM20) that allow us to mark an exon as RBM20 affected or not affected. Moreover, functional studies are undergoing for transcripts expressed by one of the genes affected by RBM20
Searching for DNA motifs that affect splicing of exons regulated by RBM20
No full textRecent studies showed that RNA binding motif protein 20 (RBM20) is involved in the regulation of the alternative splicing of several genes both in rats and humans. Mutations in RBM20 have been shown to cause human dilated cardiomyopathy. RBM20 RNA-binding site maps in the intronic sequence of the target genes in close proximity to differentially spliced exons and an overrepresentation of RBM20 RNA-binding sites in these regions was noticed. However, a detailed rule is missing.
The aim of our ongoing investigation is to find exons whose alternative splicing is affected by RBM20, and then to define sequence patterns of the RBM20 regulated exons.
RNA sequencing data of human and rat cardiomyocytes made avaible by Guo were used. Rat samples showed 3 different conditions: 3 wild type (RBM20+/+), 3 heterozygosity (RBM20+/-) and 3 deletion (RBM20-/-) samples. Human samples showed 2 different conditions: 2 control individuals (RBM20+/+) and 1 RBM20 mutated individual (RBM20-/-). The rat RGSC3.4 and human GRCh37 reference genomes were used to map the rat and the human samples, respectively, and the expression of each individual exon has been measured. An analysis was carried out to identify differentially spliced (DS) exons between RBM20 positive and negative samples.
The differential analysis between RBM20+/+ and RBM20-/- samples showed 96 DS exons (p. adj < 0.05) belonging to 33 different genes, and 1816 DS exons belonging to 657 different genes, in rat and humans, respectively. We studied the 400 nt preceding and following the sequence of the affected exons. The exon following sequence showed a greater number of RBM20 RNA-binding sites than the exon preceding sequence, and the opposite was observed for the analyzed control sequences. The enrichment analysis of novel motifs showed 2 motifs more common in case than in control sequences.
We are now evaluating the statistical significance of these observations and we are testing novel hypothesis for a more accurate definition of the RBM20 RNA-binding site
RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3
No full textRegulation of alternative splicing events is an essential step required for the expression of functional cytoskeleton and sarcomere proteins in cardiomyocytes. About 3% of idiopathic dilated cardiomyopathy cases present mutations in the RNA binding protein RBM20, a tissue specific regulator of alternative splicing. Transcripts expressed preferentially in skeletal and cardiac muscle, including TTN, CAMK2D, LDB3, LMO7, PDLIM3, RTN4, and RYR2, are RBM20-dependent splice variants. In the present study, we investigated the RBM20 involvement in post-transcriptional regulation of splicing variants expressed by Formin homology 2 domain containing 3 (FHOD3) gene. FHOD3 is a sarcomeric protein highly expressed in the cardiac tissue and required for the assembly of the contractile apparatus. Recently, FHOD3 mutations have been found associated with heart diseases. We identified novel FHOD3 splicing variants differentially expressed in human tissues and provided evidences that FHOD3 transcripts are specific RBM20 and PTBP1 targets. Furthermore, we demonstrated that the expression of RBM20 and PTBP1 promoted the alternative shift, from inclusion to exclusion, of selected FHOD3 exons. These results indicate that RBM20 and PTBP1 play a role in the actin filament functional organization mediated by FHOD3 isoforms and suggest their possible involvement in heart diseases
Interhemispheric transfer of spatial and semantic information: Electrophysiological evidence.
No full textAbstract
The goal of this study was to cast light on the existence of functional callosal channels for the interhemispheric transfer (IHT) of spatial and semantic information. To do so, we recorded event-related potentials in healthy humans while performing a primed odd-even discrimination task. Targets were visually presented numbers preceded by single-letter primes signaling the probable presentation of an odd or an even number. Primes and targets could appear either in the same or in different visual fields, thus requiring an IHT in the latter case. The P1 and N2 components were influenced by IHT of spatial information only, whereas the later N400 was influenced by IHT of both spatial and semantic information. This was not the case for the P3b, which was modulated by semantic validity only. These results provide novel evidence of the existence of a temporally separated interhemispheric exchange of spatial and semantic information
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
Association of microRNA 146a polymorphism rs2910164 and the risk of melanoma in an Italian population
No full text[No abstract available
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
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