1,721,337 research outputs found
HISTONE-DEPENDENT AND HISTONE-INDEPENDENT PATHWAYS FOR RAD9 CHROMATIN RECRUITMENT AND CHECKPOINT ACTIVATION
Full text linkMaintenance of genome stability is critical to cell survival and normal cell growth. Indeed, genome instability is a hallmark of most human cancers. To ensure the accurate transmission of genetic information to the offspring, eukaryotic cells evolved a complex network of surveillance and DNA repair mechanism, which allow the faithful transmission of genetic information throughout generations. These surveillance systems, called DNA damage checkpoints, are signal transduction cascades where the DNA damage signal is transmitted, through the action of protein kinases, to the cell cycle machinery, resulting in the temporary arrest of cell proliferation at the G1/s or at the G2/M transitions, or in the slowing down of DNA replication. Moreover checkpoint activation frequently brings about also changes in the transcritptional programme of the cell and modification in the DNA repair factors, resulting in a more efficient removal of the lesion.
Since the basic checkpoint response has been shown to be conserved, from yeast to human cells, many details of this mechanism have been outlined by genetic and biochemical means in budding and fission yeasts, thanks to their genetic versatility and experimental tractability.
The current model predicts that activation of the first checkpoint kinase in the cascade is not due to the DNA damage itself, but it requires recognition and initial processing of the lesion by some nucleases generating long 3’ ssDNA tails. The ssDNA regions are rapidly bound by the RPA complex, generating a structure that is responsible for the recruitment and activation of the apical kinase complex Mec1-Ddc2 and for the loading onto DNA of the 9-1-1 complex. Once activated, Mec1 phosphorylates different targets, among which Ddc2, the Ddc1 component of the 9-1-1 complex, histone H2A. Another Mec1 target is adaptor Rad9. Phosphorylation of Rad9, followed by its oligomerization, allows the recruitment and activation of the effector checkpoint kinase Rad53. This is a key step in the signal transduction cascade; it can be easily visualized as a hyperphosphorylated slower-mobility form by Western blotting and it is generally used as a marker to monitor checkpoint activation.
Recent work demonstrated that histone H2B-K123 ubiquitylation, carried out by Rad6-Bre1, and histone H3 methylation on lysine 79 (H3-K79), performed by Dot1, contribute to Rad9 recruitment to chromatin. Infact, it has been demonstrated that Rad9 physically interacts with methylated H3-K79 thanks to its Tudor domain. Impairment of this recruitment-pathway prevents Rad9 and Rad53 phosphorylation in G1-arrested cells and abolishes the G1-S arrest following DNA damage. Surprisingly in M-arrested cells, deletion of Dot1 or mutation of the Rad9 Tudor domain does not completely abrogate the checkpoint function and Rad53 phosphorylation after genotoxic treatment. This evidence suggests the existence of a second pathway, partially redundant with the histone dependent branch, that, in M phase, provides an alternative way for Rad9 to be recruited in the proximity of the lesion and to be phosphorylated.
We found that the replication factor Dpb11 is the keystone of this second pathway. Our data suggest that Dpb11 is held in proximity to damaged DNA through an interaction with phosphorylated 9-1-1, specifically within its Ddc1 subunit. Once recruited in the proximity of the lesion, it performs a double role: it contributes in the full activation of the apical checkpoint kinase Mec1 and it cooperates with Dot1 in the recruitment of Rad9.
In particular, we discocvered that Dpb11 physically interacts with Rad9. This interaction depends upon CDK-dependent phosphorylation of Rad9 on the Ser11 residue, at the N-terminus of the protein. We also provide evidence that the Dpb11-dependent branch of Rad9 recruitment is necessary and sufficient for checkpoint activation when the histone-dependent pathway is impaired, and it allows Rad53 phosphorylation, despite undetectable Rad9 binding on the chromatin, suggesting that Rad9 complexed with Dpb11 is not tighly linked to chromatin
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
Quali prospettive per il secondo welfare? : la crisi del welfare state tra sfide e nuove soluzioni
No full textkoamabayili/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
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