1,721,019 research outputs found
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
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
Investigating the consequences of replication fork collapse at protein-DNA barriers
No full textThe inadvertent stalling of replication forks (RFs) upon protein-DNA barrier collision may render them unable to continue DNA synthesis. Following fork collapse, DNA replication can be completed either by a canonical fork converging on the collapsed fork or by the collapsed fork restarting through a recombination-dependent process. Our knowledge of how recombination restarts collapsed forks and how fork convergence (FC) is conducted at replication fork barriers (RFBs) remains limited. Studies in Schizosaccharomyces pombe (S. pombe), using the unidirectional RFB RTS1 to induce site-specific RF collapse, have revealed some of the key factors that govern recombination-dependent replication (RDR) as well as characteristic features of the RDR process such as a propensity for the restarted replication to undergo template switching (TS) that can drive genome rearrangement. However, the list of factors that influence RDR remains incomplete. It also remains unclear whether the features of RDR that are triggered by RTS1 are similarly triggered by other RFBs. Studies using RTS1 have also provided insights into how FC at an RFB can provoke recombination that gives rise to different types of genome rearrangement. However, it remains unclear how exactly these genome rearrangements arise and what additional problems may be caused at bi-directional RFBs. In this study, the cellular response to two bi-directional site-specific protein-DNA RFBs, Tus-ter and MarBl, is investigated to explore whether key features of RDR and FC observed with RTS1 are induced by other RFBs. The findings show that Tus-ter and MarBl induce TS events but to a lesser extent than RTS1. Similar to RTS1, Tus-ter and MarBl also induce duplication-deletion (Dup-Del) rearrangements. This study investigates the genetic requirements for TS and putative Dup-Del events induced by Tus-ter. This study also investigates whether FC is likely responsible for the induction of high localised recombination rates at bi-directional RFBs. Lastly, efforts are presented to establish a new recombination reporter to facilitate the screening of a genome-wide S. pombe deletion library for genes that affect RTS1-induced recombination
Investigating DNA replication perturbance induced by CRISPR-Cas9 variants
No full textSingle-Stranded DNA breaks (SSBs) represent one of the most abundant DNA lesions occurring in the cells of living organisms. If encountered by the DNA replication machinery, SSBs can be converted into double-stranded DNA breaks (DSBs). Homologous recombination (HR) pathways are deployed to repair these DSBs and initiate replication restart. However, HR-mediated replication restart, whilst helping to ensure that DNA replication is completed prior to cell division, is a potential cause of genome instability due to the possibility of recombination between ectopic homologous sequences, and the compromised stability and fidelity of the restarted replication fork.
In this study, I have established a site- and strand-specific nicking system using CRISPR-Cas9 nicking variants (Cas9n) to investigate the formation and repair of replication associated DSBs in fission yeast. I discovered that SSBs induced by Cas9n in the leading/lagging strand template are converted into two-ended DSBs upon concerted replication fork stalling and fork convergence at the SSB. The Cas9n induced replication associated DSBs give arise to high levels of direct repeat recombination through Rad51 mediated Synthesis Dependent Strand Annealing (SDSA)/Sister Chromatid Exchange (SCE) and Rad52 mediated Single Strand Annealing (SSA). I have also shown that Cas9n induced SSBs in both leading and lagging strand templates can trigger Break-Induced Replication (BIR) and associated template switching downstream.
Other than SSBs, DNA-protein complexes are also proposed to be major impediments to ongoing DNA replication. Examples of such barriers include the programmed DNA-protein barrier RTS1 and non-programmed DNA-protein barriers such as lacO-LacI. To further investigate what happens when replication forks encounter DNA-protein complexes in fission yeast, I used catalytically dead Cas9 (Cas9d) to create a site-specific barrier. As the Cas9d-DNA complex contains an R-loop, it may mimic other R-loop containing protein complexes such as the transcription machinery and, therefore, provide a model for better understanding of transcription-replication conflicts. I found that Cas9d is only a weak barrier to DNA replication in fission yeast, yet it can strongly induce direct repeat recombination that is primarily driven by Rad51. Intriguingly, this recombination is restricted to ~2kb region adjacent to the gRNA binding site and does not lead to any recombination dependent replication (RDR) associated template switching downstream of the gRNA site. These features distinguish Cas9d from the RTS1 replication fork barrier, which causes a wider spread of recombination activity adjacent to it and high levels of template switching downstream
Investigating the molecular mechanisms of recombination-dependent replication in fission yeast
Get PDFPerturbation of DNA replication is a major cause of cancer and other pathological states causing loss of genome integrity and catastrophic chromosomal rearrangements. To guard against such disaster, mechanisms exist to process and stabilize replication forks (RFs) blocked at barriers, restart collapsed forks and ensure faithful fork merging and termination. Despite recent advances, our understanding of the molecular mechanisms that drive recombination-dependent replication at the replication fork barriers (RFBs) is far from comprehensive, and in particular we know very little about mechanisms used to govern its accuracy.
To characterize factors that are needed for the successful processing and restart of blocked RFs at the site-specific RFB Replication Termination Sequence RTS1 in Schizosaccharomyces pombe, I focused on studying a putative partner protein of the Fml1 DNA helicase called Dbl2; its orthologs can be found from yeast to human. I used a combination of yeast genetics, fluorescent microscopy and live cell imaging to investigate the role of Dbl2. Data from epistasis analysis, with key components of the homologous recombination machinery, highlights differences with a fml1â mutant and suggest that Dbl2 is involved in destabilizing the Rad51-nucleoprotein filament in conjunction with the Fbh1 DNA helicase. However, this genetic analysis also revealed that Dbl2 has functions that are independent of Fbh1 in the regulation of Rad51-independent Rad52-dependent recombination, spontaneous and induced at RTS1. This may include a role in and/or regulating other helicases such as Fml1 and Pfh1. Structureâfunction studies using a series of truncation and internal deletion mutants of Dbl2 demonstrate that the cooperative action of all regions is required for Dbl2 function to limit recombination induced at RF blocked at RTS1, to counteract Rad51 activity in the presence of Rad55 and for its nuclear localization to the multiple sites across the genome. However, only its middle region is important to confer resistance to genotoxins and genetic interaction with most Rad51 mediator proteins. In addition, I have developed expression and purification strategies for full-length Dbl2 and its functional domain and conducted preliminary experiments for the characterization of the conserved N-terminal domain DUF2439 structure.</p
Investigating the recombinational response to replication fork barriers in fission yeast
No full textTimely completion of DNA replication in each cell cycle is crucial for maintaining genomic integrity. This is often challenged by the presence of various replication fork barriers (RFBs). On collision with a RFB, the fate of the replication fork remains uncertain. In some cases, the integrity of the fork is maintained until the barrier is removed or the fork is rescued by merging with the incoming fork. However, fork stalling can cause dissociation of all of the associated replication proteins (fork collapse). If this occurs, the cellâs recombination machinery can intervene to help restart replication in a process called recombination-dependent replication (RDR).
Programmed protein-DNA barriers like the Replication Terminator Sequence-1 (RTS1) have been used to demonstrate that replication fork blockage can induce recombination. However, it remains unclear how efficiently this recombination gives rise to replication restart and whether the restarted replication fork exhibits the same fidelity as an origin-derived fork. It is also unknown whether accidental replication barriers induce recombination in the same manner as programmed barriers.
In this study, I introduce recombination reporters at various sites downstream of RTS1 to obtain information on both the fidelity and efficiency of replication restart. I find that unlike break induced replication (BIR), the restarted fork gives rise to hyper-recombination at least 75 kb downstream of the barrier. Surprisingly, fork convergence, rather than inducing recombination, acts to prevent or curtail genetic instability associated with RDR. I also investigate a number of genetic factors that have a role in either preventing or promoting genome instability associated with the progression of the restarted fork.
To compare RTS1 with an accidental protein-DNA barrier, a novel site-specific barrier system (called MarBl) was established based on the human mariner transposase, Hsmar1, binding to its transposon end. Replication fork blockage at MarBl strongly induces recombination, more so than at RTS1. This appears to be a general feature of accidental barriers as introduction of the E. coli TusB-TerB site-specific barrier in S. pombe gives rise to a similar effect. Here, I compare and contrast accidental barriers with programmed barriers. I observe that there is very little replication restart, if any, at MarBl measured by direct repeat recombination downstream. This points to the fact that accidental barriers do not trigger fork collapse in the same way as programmed RFBs and that the increased recombination that they cause may be a consequence of the inability of replication forks to terminate correctly, owing to the bi-directional nature of the barrier. Several genetic factors are assessed for their impact on MarBl-induced recombination, which further highlights both similarities and differences with RTS1-induced recombination.</p
- …
