1,721,039 research outputs found
GTP drives myosin light chain 1 interaction with the class V myosin Myo2 IQ motifs via a Sec2 RabGEF-mediated pathway
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Targeted therapy for brain tumours: role of PARP inhibitors
No full textThe prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the drug of choice for glioblastoma, or ionizing radiations. Moreover, PARP inhibitors exert cytotoxic effects in monotherapy in BRCA mutated tumours, which are defective in the homologous recombination (HR) repair. Finally, recent studies have shown that inhibition of PARP function might also induce anti-angiogenic effects which might contribute to impair tumour growth. Many clinical trials with PARP inhibitors are ongoing for the treatment of a variety of advanced solid tumours, including primary or secondary brain tumours. This review discusses the implications of targeting PARP on the design of new treatment regimens
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
Glutathione transferases and glutathionylated haemoglobin in workers exposed to low doses of 1,3 butadiene.
No full textPresentazione dei risultati di precedente studio
Myc Downregulation Increases Susceptibility to Cisplatin Throught ROS-mediated Apoptosis in M14 Human melanoma Cells
No full textbc1-2 over-expression enhances NF-kappa B activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells
No full textbcl-2 expression is often associated with poor prognosis in several types of tumors; however, the role of this molecule in breast cancer is still controversial. We found earlier that over-expression of bcl-2 in a human breast-cancer cell line (MCF7(ADR)) enhances its tumorigenicity and metastatic potential by inducing metastasis-associated properties such as increased secretion of the matrix metalloproteinase-9 (mmp-9), In the present study, we investigated the effect of bcl-2 over-expression on the activity of the transcription factor NF-kappa B, an important regulator of genes involved in tumor progression and invasion. Transient transfection experiments indicate that over-expression of bcl-2 in the MCF7(ADR) call line, enhances NF-kappa B-dependent transcriptional activity. Mobility-shift analysis revealed an increase of NF-kappa B DNA-binding in bcl-2-over expressing clones that correlated with lower levels of the NF-kappa B cytoplasmic inhibitor I kappa B alpha. Moreover, point mutations of 2 highly conserved residues within the BH1 and BH2 domains that abrogate the interaction of bcl-2 with bar, or deletion of the N-terminal BH4 domain, completely eliminate the ability of this molecule to up-regulate NF-kappa B-dependent transactivation. Since mmp-9 is a NF-kappa B-regulated gene, we also investigated whether bcl-2 overexpression up-regulated mmp-9 transcription. We found that induction of mmp-9 mRNA correlates with the activation of an mmp-9-promoter-reporter-gene construct in transient transfection assay. and a mutation of the (-600)mmp-9-NF-kappa B binding element abolishes this effect. The overall data indicate that bcl-2-mediated regulation of NF-kappa B-transcription-factor activity may represent an important mechanism for the promotion of malignant behavior in MCF-7(ADR) cells. Int J. Cancer 86:188-196, 2000. Q 2000 Willey-Liss, Inc
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