1,720,963 research outputs found
Increased levels of p21CDKN1A do not inhibit the recruitment of NER factors at DNA damage sites.
No full textP21CDK1NA is a cyclin-dependent kinase inhibitor playing multiple roles also in the DNA damage response. Therapeutic trials have been developed to contrast tumor cell proliferation, by exploiting the p21 ability to arrest the cell cycle; in particular, proteasome inhibitors increase p21 protein levels, impairing tumor cell growth. However, this approach is may be potentially dangerous because high p21 levels inhibit the apoptotic response and allow DNA repair, rendering tumor cells resistant to chemotherapy. We have investigated whether the accumulation of p21 levels, induced by the inhibitor of proteasome MG132, may affect nucleotide excision repair (NER) and apoptosis. The results have shown that MG132 induced persistent increased levels of XPC, PCNA and p21 proteins at local DNA damage sites, together with accumulation of XPG, DNA polymerase δ and CAF-1, suggesting that the presence of p21 protein did not block the recruitment of NER factors interacting with PCNA. Immunoprecipitation experiments have shown that DNA pol δ interacts with an ubiquitinated form of p21. These results indicate that p21 regulates steps of NER before degradation
Involvement of the cell cycle inhibitor p21CDKN1A in DNA repair
No full textA variety of chemical and physical agents may induce the formation of different lesions in the DNA molecule. These types of DNA damage may be genotoxic to the cells, and must be removed in order to avoid genomic instability, and to prevent cancer formation. To this end, virtually every organism has developed highly conserved genome surveillance and signaling mechanisms, collectively known as the DNA damage response. This pathway consists of DNA damage signaling cascade (cell cycle checkpoints), and of DNA repair processes able to recognize and remove a great number of DNA lesions.
Recent findings have shown that cell cycle checkpoints and DNA repair systems are strictly connected each other. However, the role and the molecular mechanisms underlying these connections are not yet completely understood. Among cell cycle regulatory proteins that are activated following DNA damage, the cyclin-dependent kinase inhibitor p21CDKN1A plays fundamental roles in the DNA damage response by inducing cell cycle arrest, direct inhibition of DNA synthesis, as well as by regulating transcription and apoptosis. During the last years, several lines of evidence have also indicated that p21 may be directly involved in DNA repair. Participation of p21 in DNA repair pathways, like nucleotide excision repair (NER), and base excision repair (BER), is thought to occur thanks to its interaction with Proliferating Cell Nuclear Antigen (PCNA), a crucial protein involved both in DNA replication and repair. In addition, a direct involvement of p21 in DNA trans-lesion synthesis, has been postulated to keep within low levels the mutagenesis intrinsic in this process.
In this review, all relevant findings supporting the participation of p21 protein in NER and BER will be presented. In particular, the ability of p21 to interact with PCNA seems to be required for regulating interaction of DNA repair factors with PCNA. Examples of this role will be discussed together with other aspects of the DNA damage response in which p21 is also involved. A special attention will be given to the dynamics of p21 recruitment to sites of DNA damage. In fact, a common feature of checkpoint and DNA repair factors is their accumulation at nuclear sites where DNA damage has occurred. The involvement of p21 in various DNA repair pathways supports its important function of protein barrier against genome instability
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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