1,720,991 research outputs found
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
The Circuitry Underlying Rod Bipolar Cell Sensitization
No full textDim light vision requires the dopamine D1 receptor for the sensitization of rod bipolar cells by GABA. However, the circuit behind this mechanism is poorly defined. We used electroretinogram recordings of mice with genetic and pharmacological manipulations to investigate the identity of the cells in the circuit controlling rod bipolar cell sensitivity. We found that tonic GABA input onto rod bipolar cells comes from a wide-field amacrine cell rather than horizontal cells. The output of this wide-field amacrine cell is directly regulated by voltage-gated sodium channels and dopamine-dampened serial inhibition, providing multiple regulatory sites for adaptation in the rod system.</p
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
Interrogating Chromatin Dynamics Surrounding a DNA Double-Strand Break and Ensuing Non-Homologous End-Joining Mediated Repair
No full textThe DNA double-strand break (DSB) is one of the most toxic genomic lesions that can occur in any living cell. Failure to repair DSBs results in cell cycle arrest and ultimately programmed cell death, while improper repair can lead to profound alterations or loss of genomic information through translocations, inversions, deletions and other genomic aberrations. Although the molecular events required for the repair of double-strand breaks (DSB) have been well characterized, the role of epigenetic processes in the recognition and repair of DSBs has only been investigated at low resolution. I tested several site-specific DSB induction systems and found that that the HO endonuclease was able to rapidly and synchronously induce a site-specific DSB in Saccharomyces cerevisiae upstream of the PHO5 locus. This region of the genome is recognized for its chromatin organization, which is comprised of well-positioned nucleosomes. Utilizing MNase digestion of chromatin followed by paired-end fragment sequencing I was able to interrogate the order of chromatin changes that occur immediately following a DSB by generating a base-pair resolution map of the chromatin landscape. In wild-type cells, the first nucleosome left of the break was rapidly evicted. The eviction of this flanking nucleosome was dynamic and proceeded through an early intermediate chromatin structure where the nucleosome was repositioned in the adjacent linker DNA. Other nucleosomes bordering the break were also shifted away from the break; however, their loss was more gradual. These local changes preceded a broader loss of chromatin organization and nucleosome eviction that was marked by increased MNase sensitivity in the regions ~8 kb on each side of the break. While the broad loss of chromatin organization was dependent on the end-processing complex, Mre11-Rad50-Xrs2 (MRX), the early remodeling and repositioning of the nucleosome adjacent to the break was independent of the MRX and yKU70/80 complexes. I also examined the temporal dynamics of non-homologous end joining (NHEJ) mediated repair in a G1-arrested population. Concomitant with DSB repair, I observed the re-deposition and precise re-positioning of nucleosomes at the originally occupied positions. This re-establishment of the pre-lesion chromatin landscape suggests that a DNA replication-independent mechanism exists in G1 cells to preserve epigenome organization following DSB repair.</p
Genome-Wide Dynamics of Chromatin Maturation Following DNA Replication
No full textAll DNA-templated events, including replication and gene transcription, occur in the context of the local chromatin environment. The passage of the replication machinery results in disassembly of chromatin, which must be re-assembled behind the replication fork to re-establish the epigenetic state of the cell. Many of the factors and mechanisms regulating DNA replication and chromatin assembly have been identified from elegant in vitro biochemical experiments, work in model systems like Saccharomyces cerevisiae, or novel proteomic approaches. In spite of current advances in the field, it is still not clear how the chromatin landscape is organized and re-assembled during this process.Current methods, while informative, lack the genome-wide base-pair resolution required to assess the dynamics of chromatin assembly and maturation in a spatial-temporal manner. To overcome the limitations of these studies, I have taken advantage of an epigenome mapping technique based on micrococcal nuclease (MNase) digestion followed by paired-end sequencing. This approach facilitates the analysis of chromatin structure by capturing not only nucleosomes, but also smaller DNA binding protein footprints in a factor-agnostic manner. I have developed a technique based on this approach that generates Nascent Chromatin Occupancy Profiles (NCOPs) to study the dynamics of chromatin assembly following passage of the DNA replication fork at a genome-wide level and at single base-pair resolution in S. cerevisiae. It employs a nucleoside analog to specifically enrich for nascent chromatin, which can be captured following a chase over different periods of time. Thus, NCOPs resolve the structure of nascent and mature chromatin, facilitating the analysis of chromatin maturation across the entire genome. Using NCOPs, I provide a comprehensive description of the maturation process across different genomic regions and the dynamics of small DNA binding factor association with nascent and mature chromatin states. Our results support previous work characterizing the structure of nascent chromatin as being more disorganized and having poorly positioned nucleosomes. Importantly, using positioning and occupancy scores, I provide new details on the structure of nascent and mature chromatin at intergenic regions, including replication origins, and at highly transcribed and poorly transcribed genes. I uncovered that local epigenetic footprints have the potential to shape the dynamics of chromatin assembly, generating a chromatin maturation landscape that is dependent on the parental chromatin. Finally, I resolved patterns of transcription factor occupancy with nascent and mature chromatin, and observed transient factor association in the nascent state. In all, this work provides insight into the dynamics of chromatin assembly, and allows for genome-wide and base-pair resolution investigation of chromatin maturation. The genomic and bioinformatic approaches developed here open the door for further investigation of the dynamics of epigenetic inheritance and the role of known and unknown players in re-establishing the eukaryotic epigenome following passage of the DNA replication fork.</p
Chromatin Dynamics and Regulation of the Helicase During Replication Initiation
No full textDNA replication is an intricate process within eukaryotic cells that must be precisely executed to preserve genetic information. This process begins at multiple start sites, or origins of replication, along each chromosome which are selected, licensed, and activated through cell-cycle regulated steps. Powerful reconstitution studies have identified the proteins involved in these processes, but they do not fully recapitulate the nuclear environment. Within the nucleus, the genome is organized in a chromatin structure consisting of DNA and all associated factors. At origins of replication, local chromatin contributes to origin identity and activation, but the precise chromatin dynamics that occur at these sites during helicase activation and initial DNA unwinding have not been fully explored. Additionally, how these steps are regulated to ensure genomic stability remain unstudied within the context of chromatin.To address these questions, I have developed a conditional system that removes polymerase α function to capture helicase activation at replication origins in the budding yeast. Under restrictive conditions, these cells (cdc17-ts-FRB) do not initiate replication. When allowed to recover, replication appears to initiate outside origins, necessitating a delay in G2/M phase to repair unreplicated gaps at origins. To investigate origin chromatin and helicase movement prior to replication, I used MNase chromatin profiling alongside ChIP-seq for various replication factors. Chromatin in a 1 kb region around early, efficient replication origins is disrupted under restrictive conditions. The active helicase unwinds DNA out to 1 kb from these origins and is likely the source of the chromatin disruption. I next used the cdc17-ts-FRB conditional system to investigate the regulation of helicase progression in the absence of replication. I first tested whether the intra-S-phase checkpoint had a role in stalling the helicase 1 kb from the origin. Though removing checkpoint activation distributed helicase movement and chromatin disruption to late, inefficient origins, it did not alter the distance the helicase progressed from the origin. Instead, the helicase stalls as it leaves the AT-rich origin region and encounters sequences with higher GC content. These results provide in vivo support for the recently proposed “dead man’s switch” model for decreased helicase processivity when uncoupled from replication.Helicase activation and origin unwinding are essential steps during DNA replication that expose ssDNA and thus have the potential to cause genomic instability. My studies have captured origin chromatin dynamics caused by an active helicase unwinding DNA, and have contributed evidence that the helicase may be intrinsically less processive in the absence of leading strand synthesis. These results may have implications for the mechanisms underlying human diseases involving polymerase α, and contribute to our growing understanding of how the eukaryotic cell preserves the integrity of the genome.</p
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