1,721,019 research outputs found
Notch signaling involvement in endothelial responses to inflammation: Jagged1 and Notch1 mediate IL-1beta-Induced up-regulation of adhesion molecules
Full text linkObiettivo--Il signaling di Notch, attraverso l’attivazione dei recettori Notch1 e Notch4, gioca un ruolo chiave nella determinazione e nell’omeostasi dell’endotelio. Il TNFa determina la down-regolazione di Notch4 e del target gene Hes1, e questa modulazione causa la perdita della quiescenza e l’induzione della molecola di adesione vasale (VCAM-1) nelle cellule endoteliali (ECs). Questo studio mira ad investigare la regolazione dei componenti del signaling di Notch indotta dall’IL-1b ed il loro coinvolgimento nell’up-regolazione delle molecole di adesione.
Metodi e Risultati--Abbiamo dimostrato che l’IL-1b induce una forte up-regolazione di Jagged1, e mentre l’attivazione di Notch4 diminuisce, la forma attiva di Notch1 (Notch1ICD) rimane costante. La complessiva inibizione del signaling di Notch, attraverso un inibitore della g-secretasi, determina una riduzione nell’up-regolazione di VCAM-1 indotta dall’IL-1b. Inoltre, il silenziamento di Jagged1 ha un effetto negativo sull’up-regolazione delle molecole di adesione indotta dall’IL-1b e il doppio silenziamento di Jagged1 e Notch1 determina un effetto ancora maggiore. In aggiunta, la forzata over-espressione di Notch1ICD induce l’espressione di VCAM-1, e questo effetto aumenta dopo il trattamento con l’IL-1b. Nelle cellule over-esprimenti Notch1ICD, inibendo chimicamente la traslocazione nucleare di NF-kB indotta dall’IL-1b, non si riduce significativamente l’up-regolazione di VCAM-1. In fine, l’over-espressione di Hes1, durante il trattamento con l’IL-1b, inibisce l’up-regolazione delle molecole di adesione e reprime la trascrizione di Jagged1, indicando un loop regolativo negativo tra i componenti del signaling di Notch.
Conclusioni—Complessivamente i risultati indicano che Jagged1 segnala attraverso Notch1, e Notch1 e’ il recettore piu’ importante nella risposta infiammatoria delle ECs. Inoltre, in presenza di Notch1 l’induzione delle molecole di adesione risulta solo parzialmente dipendente da NF-kB.Objective--Notch signaling plays a key role in endothelial determination and homeostasis through Notch 1 and Notch 4 receptors. In endothelial cells (ECs) the TNFa determines the down-regulation of Notch4 and Hes1 and this modulation are associated with the loss of quiescence and the up-regulation of vascular cell adhesion molecules-1 (VCAM-1), This study investigated the regulation of Notch signaling components upon IL-1β induction and their implication in the up-regulation of adhesion molecules.
Methods and Results-- We showed that IL-1β induced a strong up-regulation of the Notch ligand Jagged1. Strikingly, while Notch4 activation decreased, Notch1 active form (Notch1ICD) remained constant. The global inhibition of Notch activation through a g-secretase inhibitor resulted in reduction of IL-1β-induced VCAM-1 up-regulation. Moreover, the silencing of Jagged1 partially affected the up-regulation of adhesion molecules induced by IL-1b, and the double silencing of Jagged1 and Notch1 led to a higher reduction of the adhesion molecules expression after IL-1β treatment. Interestingly, Notch1ICD forced expression induced VCAM-1 expression in ECs and increased the up-regulation induced by IL-1β treatment. Chemical inhibition of the NF-kB nuclear translocation induced by IL-1β treatment did not significantly reduce VCAM-1 expression in Notch1ICD expressing cells. Finally, Hes1 over-expression during IL-1β treatment inhibited the up-regulation of adhesion molecules and, concomitantly, repressed Jagged1 trascription, suggesting a negative regulative loop between Notch signaling component.
Conclusions--All together our results indicate that, Jagged1 sustains Notch1 activation that specifies the effects of IL-1β. Thus, Notch1 is the most important receptor involved in inflammatory responses of ECs, and its function is, at least in part, NF-kB-dependent
ANALISI DI ETEROPLASMIE MEDIANTE DHPLC IN UN CASO DI IDENTIFICAZIONE PERSONALE
No full textIl sequenziamento del DNA mitocondriale (mtDNA) è un valido approccio per la tipizzazione dei campioni biologici degradati caratterizzati da uno scarso contenuto di DNA genomico. Ci sono diversi aspetti analitici da considerare nella validazione dei risultati ottenuti mediante analisi dell’mtDNA. Una delle problematiche è connessa al fenomeno dell’eteroplasmia che è quella condizione in cui due o più aplotipi sono presenti in un singolo individuo, cellula o mitocondrio. Le eteroplasmie possono essere di sequenza e di lunghezza. Quest’ultime rendono difficile l’interpretazione dei risultati in quanto determinano uno slittamento del modulo di lettura della sequenza a valle del punto eteroplasmico. Inoltre il sequenziamento diretto, la metodica di prima scelta nell’analisi forense dell’mtDNA, non permette di determinare la lunghezza della variazione nucleotidica delle molecole eteroplasmiche. Nell’identificazione forense la presenza di eteroplasmie influenza l’eventuale corrispondenza tra il campione biologico in esame ed i putativi parenti materni in quanto gli aplotipi a confronto sembrano differire. In questo studio descriviamo la positiva identificazione di un resto scheletrico, il cui profilo mitocondriale presentava un’eteroplasmia di lunghezza, che è stato comparato con i profili ottenuti rispettivamente dalla madre e dal fratello. L’eteroplasmia di lunghezza è stata risolta mediante analisi di cromatografia liquida denaturante ad alta pressione (DHPLC) che ha permesso di discriminare le molecole eteroplasmiche sulla base della loro differenza di lunghezza. La DHPLC è una metodologia largamente utilizzata nel campo della ricerca biologica per rilevare mutazioni genetiche, ma l’estrema sensibilità e le ampie possibilità d’applicazione nell’analisi del DNA la rendono uno strumento utile nel campo dell’identificazione genetica forense
IDENTIFICATION OF HUMAN BODY FLUID: COMPARISON BETWEEN TWO COMMERCIAL KITS FOR DETENCTION OF SEMEN
No full textViral Manipulation of the Host Epigenome as a Driver of Virus-Induced Oncogenesis
Full text linkTumorigenesis due to viral infection accounts for a high fraction of the total global cancer burden (15-20%) of all human cancers. A comprehensive understanding of the mechanisms by which viral infection leads to tumor development is extremely important. One of the main mecha-nisms by which viruses induce host cell proliferation programs is through controlling the host’s epigenetic machinery. In this review, we dissect the epigenetic pathways through which oncogenic viruses can integrate their genome into host cell chromosomes and lead to tumor progression. In addition, we highlight the potential use of drugs based on histone modifiers in reducing the global impact of cancer development due to viral infection
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
- …
