1,720,988 research outputs found
Biochemical approaches to characterize targets responsible for acrylamide-induced inhibition of topoisomerase II
No full textVinyl monomer acrylamide (AA), generally used in numerous industrial applications, has been classified by the International Agency for Research on Cancer (IARC) as “probably carcinogenic to humans” (group 2A), but the molecular mechanism underlying its genotoxicity has not fully known.
Previously, we observed that Acrylamide (AA) was able to antagonize in vivo the citotoxicity of well know poison etoposide suggesting that topoisomerase II (Topo II) activity was affected by AA.
In the current studies we investigated the inhibitory activity of acrylamide toward topoisomerase II by performing tests in vitro
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
Evaluation of DNA damage in murine fibroblasts treated with cigarette smoke condensate
No full textCSC is a complex chemical mixture containing about 4800 compounds, many of them have cytotoxic and mutagenic activities on mammalian cells. Most of these compounds are able to interact with DNA at different levels. Cells may respond to DNA damage by following different pathways, such as the DNA repair processes and the cell cycle and DNA damage checkpoint activation.
To the aim to evaluate the biological effects of CSC on cells, alkaline comet assay and flow cytofluorimetry were used to examine DNA damage/repair and cell cycle progression. All experiments were performed by using CSC from standard cigarettes in the range of doses 30-180g/ml and Swiss 3T3 murine fibroblasts.
Results obtained by comet assay showed that CSC induces DNA strand breaks, significantly higher after 90 min of treatment than 3hrs. This difference, particularly evident at 100 and 150g/ml, it is probably due to a fast repair that can be explained by the oxidative component of the DNA damage CSC-induced. To clarify these results, further investigations on the evaluation of the oxidative damage are in progress by applying two different methods. one is the detection of the oxidised bases on the DNA by using the modified protocol of Comet assay with FPG and endo III, the second is the analysis of the intracellular levels of ROS, measured as the ability of treated cells to oxidise a fluorogenic dye, is going to be carried out.
Previous results of long-term survival showed that cells lose their ability to form colonies in dose-dependent manner, after 24hrs of CSC treatment and 168 hrs of culture. However, the cytofluorimetric analysis showed that a fraction of cells, blocked in G2/M immediately after 24hrs of treatment, are gradually granted to continue the cell cycle, after incubation for further 6hrs in medium CSC-free. Further investigations on the cell cycle alteration are on going
Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability
Full text linkThe mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylation that persists for many population doublings after the treatment.
In V79 cell populations, progressive aneuploidy increases were notable by 50 cell generations after a 24 hr exposure to 1-10 uM arsenite. Dicentric chromosomes and/or telomeric associations, as well as complex chromosome rearrangements, occurred by 90 cells generations post treatment; and mutator and transformed phenotypes began to appear thereafter. This increasing genomic instability correlated with modifications of global DNA methylation patterns in V79 cells evaluated by 5-methylcytosine antibody binding and MeSAP-PCR. The results show that short-term exposure to arsenite induced an apparent genome hypomethylating effect within a short time after exposure.
In identical protocols using human HaCaT keratinocytes exposed to low doses of arsenite (0.05-0.1 M) for 24 hr, genomewide methylation levels were measured by LINE1 pyrosequencing and gene-specific methylation status was assessed by Methylation-Specific-PCR for up to 40 generations post exposure. Global demethylation following treatment was supported by preliminary LINE-1 studies. Moreover, the study of gene-specific MSP and determination of expression levels by RT-PCR of several genes (p16, hMLH1, hMSH2, DNMT1, DNMT3a and DNMT3b) demonstrated that hMSH2 gene was epigenetically regulated by arsenite and that down regulation of DNMT3a and DNMT3b genes occurred in an arsenite dose-dependent manner.
The results reported here demonstrate that acute 24 hr arsenic exposure promptly induces genome wide DNA hypomethylation, and support the hypothesis that the cells continue to undergo epigenetic reprogramming both at the gene and genomic levels in the absence of further arsenite treatment; thus likely contributing to long-lasting genomic instability that manifests as aberrant chromosomal, mutator and cell transformation effects
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
Il PTHrP [38-94]-amide è un fattore “DNA-binding”: dati citogenetica e molecolari ed effetto biologico su cellule epiteliali mammarie immortalizzate e neoplastiche
No full textStudio sull'induzione di danno al DNA, micronuclei ed alterazioni del ciclo cellulare da condensato di sigaretta
No full textNumerosi studi confermano l’associazione tra fumo di sigaretta e insorgenza di patologie-polmonari, cardiovascolari e tumori. Il fumo, infatti, contiene diversi composti mutageni c cancerogeni. Premesso che non esiste una sigaretta sicura, è comunque possibile attuare strategie per caratterizzare e ridurre il rischio. In questo studio, abbiamo utilizzato test in vitro per investigare i possibili meccanismi d’azione del condensato di sigaretta (CSC), ovvero la frazione particolata del fumo, assorbita nei polmoni del fumatore e successivamente metabolizzata. Analisi precedenti avevano dimostrato che il CSC, dopo 24h di trattamento induce decremento della vitalità delle cellule Swiss3T3 (IC50 = 130 μg/ml), inibizione dell’efficienza di clonaggio (circa il 60% a`50 μg/ml) e attivazione delle caspasi già a partire dalla prima dose testata (25 μg/ml). La natura degli effetti genotossici del CSC è stata analizzata con il Comet assay che ha evidenziato la capacità del CSC di indurre rotture a singolo e doppio filamento del DNA, dopo trattamenti per 90min e 3 h, a partire dalla dose di 100 μg/ml (p<0.001 Kruskall-Wallis). Il significativo aumento (p<0.001 Mann-Whitney U-test`) delle rotture al DNA è stato osservato dopo 90 min di esposizione a 100 e 150 μg/ml di CSC lascia ipotizzare che la componente ossidativa del danno indotto da CSC venga rapidamente riparata. Il saggio del micronucleo è stato effettuato su cellule trattate con 30 μg/ml di CSC e osservate immediatamente dopo il trattamento e fino a 120h di coltura in terreno completo senza condensato. I risultati ottenuti hanno evidenziato un aumento significativo (p<0.005 t-Student) di cellule micronucleate dopo 72h di recupero. Utilizzando anticorpi anti-nucleari (ANA test) contro il cinetocore è stato possibile mettere in evidenza che il trattamento con CSC esplica prevalentemente un effetto clastogeno. La comparsa dei micnonuclei solo dopo 72h dal trattamento sembra essere correlata al ritardo nella progressione del ciclo cellulare come indicano sia il decremento di cellule in mitosi osservato subito dopo il trattamento, sia l’accumulo dose-dipendente di cellule in G2/M
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