1,720,961 research outputs found
MECHANISMS PRESERVING GENOME INTEGRITY IN SACCHAROMYCES CEREVISIAE
Get PDFThe integrity of the genome is continuously jeopardized by endogenous reactive byproducts of cellular metabolism and genotoxic insults by environmental agents, as well as by the DNA transactions (replication, transcription and recombination) required for cell survival and proliferation. Failure of the mechanisms deputed to the maintenance of genome integrity leads to genome instability, which is a hallmark of cancer and a driving force of tumorigenesis. To fully understand the mechanisms leading to genome instability and the cellular pathways counteracting them, three basic tasks must be achieved: i) identify all the genes implicated in the control of genome integrity; ii) unravel their biological role; iii) define the mechanistic molecular details of the processes in which they are implicated. This thesis describes work performed in the budding yeast Saccharomyces cerevisiae to explore the genome stability landscape at all these three levels. This model system is extremely useful for two main reasons: a) its high genetic tractability allows the application of genome-wide genetic screenings; b) the large conservation of the genome integrity pathways allows to extend the findings obtained in yeast to other eukaryotic organisms.
We performed a genome-wide screen, based on the overexpression of the DDC2 DNA damage checkpoint gene in the yeast deletion collection, to identify genome stability genes on the basis of spontaneous accumulation of endogenous DNA damage in the corresponding mutant strains. Our screen identified several genes implicated in the control of genome integrity, highlighting, in particular, a key role for pathways protecting against oxidative stress. We present here the preliminary characterization of a new genome integrity gene, VID22.
We also investigated the mechanisms counteracting a newly discovered source of genome instability, namely ribonucleotides (rNTPs) incorporated in genomic DNA during replication. We uncovered a role for RNase H enzymes, template switch pathways and Pol ζ translesion polymerase in protecting from misincorporated rNTPs. Given that mutations in any of the three human RNase H2 subunits were proven to cause Aicardi-Goutiéres Syndrome, these results might contribute to shed light on the complex and largely unknown pathogenetic mechanism of this rare genetic disease.
Finally, we studied the molecular details underlying the role of Rad9 mediator protein in DNA damage checkpoint activation, exploring the dynamics of Rad9 dimerization, chromatin binding, CDK-dependent phosphorylation and checkpoint activation in G1 and M phases of the cell cycle; in particular, we characterized an M-phase specific pathway for checkpoint activation which is relies on Rad9-Dpb11 interaction
Fluid-Structure Interaction and Co-Simulation: Analysis of a Beam-Supported Sphere for VIV Application
No full textThe recent developments in numerical tools and computing resources seem to provide a suitable environment to perform numerical analyses of Fluid-Structure Interaction problems. The Co-Simulation technique, in particular, develops the idea of coupling a CFD software with a structural one in order to simulate complex FSI phenomena with a partitioned approach, stressing the concept of software modularity. In this way, it is possible to adopt software tools at the cutting edge of technology. Nonetheless, several difficulties may arise in the choice of the partitioning scheme and of the algorithmic details for the step-by-step time integration.
This paper deals with the application of the Co-Simulation technique to a benchmark case experimentally investigated in previous works: the vortex-induced vibrations (VIV) of a beam supported sphere (that is, a sphere fixed to the end of a slender cantilever beam) in a free surface flow. This problem is challenging although apparently simple and it seems quite absent from literature so far. In this paper, the computational issues are thoroughly investigated and the model is validated by comparison with the experimental data. In this way, a robust framework is created in order to deal with VIV problems
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
RNaseH2 plays a role in the maintenance of genome stability
No full textRibonuclease H (RNaseH) is a family of evolutionally conserved enzymes capable of cleaving the RNA moiety in RNA:DNA hybrid molecules. Eukaryotic cells are
provided with RNaseHI and RnaseH2 activities. The main differences between these two enzymes rest in substrate specificity. In fact only RNaseH2 is capable to recognize and cleave a single ribonucleotide in a duplex DNA molecule. Mutations in the RNaseH2 enzyme, are found in a subset of patients suffering of a rare genetic
disease, called Aicardi-Goutières Syndrome (AGS).
RNA:DNA hybrids are transient intermediates occurring during several biological processes, such as DNA replication, telomere metabolism, retrovirus replication, retroelements mobilization and transcription (i.e. R-loops). These hybrid molecules are physiologically short-lived, but in some conditions they can generate pathological structures that need to be tightly controlled in order to avoid an increase in genomic instability that is known to be linked to cancer predisposition.
We are studying the role of RNaseH in controlling genome integrity in normal and replication stress conditions, using S.cerevisiae cells as a model system. Our results indicate that yeast RNaseH mutant cells are sensitive to genotoxic treatments. We have characterized the biological process responsible for this phenotype and we have identified the molecular pathways that allows survival of the RNaseH mutants in the presence of replication stress
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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