1,720,973 research outputs found
Regolazione epigenetica della Trombomodulina e del Tumor Necrosis Factor mediata da PARP-1 nel mesotelioma maligno
No full textIl cancro esercita un profondo impatto sul sistema emostatico dell’organismo, portando ad uno stato di ipercoagulabilità, che può condurre a complicanze trombotiche. Tra i tumori solidi, il mesotelioma maligno (tumore associato all’esposizione all’amianto) è tra quelli maggiormente interessati da complicanze trombotiche. La trombo-patogenesi è scatenata dal rilascio, da parte delle cellule tumorali, di fattori pro-coagulanti ed infiammatori, che contribuiscono al mantenimento dello stato di ipercoagulabilità. Il Tumor Necrosis Factor (TNF-α) è la citochina che più influisce sul sistema emostatico, mediante una down regolazione delle funzioni anti-coagulanti, quali l’inibizione della Trombomodulina (TM), un anti-coagulante naturale coinvolto in vari processi patologici, inclusi trombosi, infiammazione e cancro. Una ridotta o assente espressione di TM è associata con una prognosi drammatica del tumore.
In questo studio, abbiamo analizzato l’espressione di TM e del TNF-α e abbiamo osservato una ridotta espressione di entrambi i geni in campioni di biopsie con mesotelioma maligno (MM) rispetto ai tessuti pleurici sani di controllo (NM). Successivamente, abbiamo indagato il ruolo dell’epigenetica nel silenziamento di questi due geni, con maggior attenzione sull’analisi dei profili di metilazione dei rispettivi promotori, che sono risultati entrambi ipermetilati nei campioni bioptici MM, ma non in quelli sani NM. Il coinvolgimento della metilazione nel silenziamento di TM e TNF-α è stato confermato anche in vitro: le linee cellulari mesoteliali immortalizzate (Met5A) e quelle di mesotelioma maligno (H28) sono state trattate con l’agente demetilante 5’-Aza deossicitidina (5’aza dC) e con l’inibitore delle deacetilasi Tricostatna (TSA). In seguito al trattamento con 5’aza dC, sia TM sia TNF-α erano drasticamente ripristinati nelle cellule H28 ma non nelle Met5A (dove i trattamenti non avevano alcun effetto). Solo per il TNF-α abbiamo osservato una significativa riespressione anche in seguito al trattamento combinato 5’aza dC + TSA nelle cellule H28, facendo ipotizzare un possibile coinvolgimento anche dell’acetilazione nel silenziamento del TNF-α. Infine, abbiamo analizzato il possibile ruolo della Poli(ADP)-ribosio polimerasi (PARP-1) come regolatore epigenetico di questi due geni, valutando gli effetti del suo silenziamento sull’espressione di TM e TNF-α nelle linee cellulari Met5A e H28. Nelle Met5A, il silenziamento di PARP-1 determinava una forte riduzione di TM e di TNF-α, corrispondente ad un profilo di ipermetilazione del loro promotore; al contrario, nelle H28, il silenziamento di PARP-1 determinava una significativa riespressione di TM e una forte riduzione di TNF-α, corrispondente ad un profilo di ipometilazione e di ipermetilazione, rispettivamente.
Da questo studio è emerso un chiaro ruolo della metilazione nella regolazione dell’espressione di TM nel mesotelioma maligno e questo meccanismo sembrerebbe essere mediato da PARP-1, che esercita un effetto contrario sull’espressione di TM, nelle cellule di controllo rispetto a quelle tumorali. Più controverso è il meccanismo di regolazione epigenetica del TNF-α, in quanto la metilazione potrebbe non essere il solo meccanismo epigenetico coinvolto; si dovrebbe indagare anche il possibile ruolo dell’acetilazione e l’eventuale coinvolgimento di PARP-1 nell’espressione di questo gene, nel mesotelioma maligno
Expression of thrombomodulin in malignant pleural mesothelioma
No full textThe malignant mesothelioma (MM) is often complicated by thromboembolic episodes, with thrombomodulin (TM) playing a role in the anti-coagulant process. We analyzed TM expression in biopsies of MM patients and in normal mesothelial tissue. The role of DNA methylation-associated gene silencing in TM expression was investigated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by their treatment with 5-aza-2’-deoxycytidine while the epigenetic agent did not affect TM expression in Met-5A cells. Methylation of the TM promoter is responsible for silencing of TM expression in MM tissue
Unexplained fetal loss: the fetal side of thrombophilia.
No full textCarrier status of the fetus for factor V polymorphism or double homozygosity for mutant alleles of the PAI-1 4 G/4
G and MTHFR T677 T polymorphisms must be considered risk factors for intrauterine fetal death. The clinical
implications of these data need to be addressed in a prospective study to confirm our preliminary data and to answer
the question of whether or not double homozygous individuals should be treated with low molecular-weight
heparin and/or low-dose aspirin
Asbestos exposure affects poly(ADP-Ribose) polymerase-1 activity: role in the asbestos-induced carcinogenesis
No full text
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
Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism
No full textMalignant mesothelioma (MM) is often complicated by thromboembolic episodes, with thrombomodulin (TM) playing a critical role in the anticoagulant process. Heterogeneous expression of TM has been observed in cancer, and low or no TM expression in cancer cells is associated with poor prognosis. In this study, we analyzed TM expression in biopsies of MM patients and compared them with normal mesothelial tissue. The role of DNA methylation-associated gene silencing in TM expression was investigated. To evaluate poly(ADP-ribose) polymerase-1 (PARP1) as responsible for gene promoter epigenetic modifications, nonmalignant mesothelial cells (Met-5A) and MM cells (H28) were silenced for PARP1 and the DNA methylation/acetylation-associated TM expression evaluated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by their treatment with 5-aza-2'-deoxycytidine and, to a lesser extent, with trichostatin, whereas the epigenetic agents did not affect TM expression in Met-5A cells. Silencing of PARP1 resulted in a strong down-regulation of TM expression in Met-5A cells, while restoring TM expression in H28 cells. PARP1 silencing induced TM promoter methylation in Met-5A cells and demethylation in MM cells, and this was paralleled by corresponding changes in the DNA methyltransferase activity. We propose that methylation of the TM promoter is responsible for silencing of TM expression in MM tissue, a process that is regulated by PARP1.No Full Tex
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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