1,721,132 research outputs found

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Global repair is the primary nucleotide excision repair subpathway for the removal of pyrimidine-pyrimidone (6-4) damage from the Arabidopsis genome

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    Abstract Ultraviolet (UV) component of solar radiation impairs genome stability by inducing the formation of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] in plant genomes. (6-4)PPs disrupt growth and development by interfering with transcription and DNA replication. To resist UV stress, plants employ both photoreactivation and nucleotide excision repair that excises oligonucleotide containing (6-4)PPs through two subpathways: global and transcription-coupled excision repair (TCR). Here, we analyzed the genome-wide excision repair-mediated repair of (6-4)PPs in Arabidopsis thaliana and found that (6-4)PPs can be repaired by TCR; however, the main subpathway to remove (6-4)PPs from the genome is global repair. Our analysis showed that open chromatin genome regions are more rapidly repaired than heterochromatin regions, and the repair level peaks at the promoter, transcription start site and transcription end site of genes. Our study revealed that the repair of (6-4)PP in plants showed a distinct genome-wide repair profile compared to the repair of other major UV-induced DNA lesion called cyclobutane pyrimidine dimers (CPDs)

    Variations on the Author

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    “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

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    We 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

    Genetic and biochemical analysis of prokaryotic members from the photolyase/cryptochrome family

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    Photolyase and cryptochrome comprise a family of structurally related bluelight photoreceptors. Photolyase repairs UV damaged DNA and cryptochromes mediate a variety of growth and adaptive responses. In this study, three genes, phr, cry1, and cry2, belonging to the photolyase/cryptochrome blue-light photoreceptor family in the V. cholerae genome were biochemically and genetically characterized. All three proteins contained the folate and flavin cofactors. One of these proteins, VcPhr, was found to be a CPD photolyase belonging the Class I photolyases. VcCry1 was found to have a small amount of CPD photolyase activity and belongs to the DASH subfamily. VcCry2 belongs to the DASH-related subfamily. Additionally, I present evidence of a new class of CPD photolyases, Class III photolyases. I have also performed a thorough phylogenetic analysis of the superfamily and have identified conserved motifs unique to individual subclasses and the tertiary location of the conserved regions. I have proposed reclassifying DASH cryptochromes as a novel class of photolyases. Also, presented is the homo- and heterodimerization of vertebrate cryptochromes. Additionally the ancient origins of vertebrate-like cryptochromes were traced back to over one billion years ago

    Understanding the role of Claspin in DNA damage checkpoints

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    DNA damage and replication checkpoints are signal transduction pathways that provide constant surveillance to maintain genome integrity. Checkpoints control a variety of cellular responses including DNA repair, chromatin remodeling and gene transcription. Claspin is an essential protein for the ATR-dependent activation of the DNA replication checkpoint response in Xenopus and human cells. The presence of stalled replication forks leads to phosphorylation of Claspin in both of the organisms and phosphorylated Claspin interacts with Chk1 and this interaction is essential for phosphorylation of Chk1 and checkpoint activation. Here we describe the purification and characterization of human Claspin. The protein has a ring-like structure and binds with high affinity to branched DNA molecules. These findings suggest that Claspin may be a component of the replication ensemble and plays a role in the replication checkpoint by directly associating with replication forks and with the various branched DNA structures likely to form at stalled replication forks due to DNA damage. In addition, we analyzed the importance of Claspin DNA binding for Chk1 activation by testing whether Claspin recruits Chk1 to DNA. These studies led to identification of Chk1 DNA binding activity. Chk1 possesses low DNA binding affinity to certain branched DNA structures and Claspin does not recruit Chk1 to DNA

    Interactions of Claspin with replication and checkpoint proteins

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    The DNA damage and replication checkpoint ensures genome stability by monitoring DNA replication and the integrity of the genetic material. In the presence of DNA damage or replication stress, the checkpoint is activated. The activation of checkpoint grants time for cells to repair the damage and to overcome replication stress. Activation of the checkpoint requires phosphorylation of several important targets, such as checkpoint effector transcription factor p53 and checkpoint transducer kinase Chk1. The mediator protein Claspin was shown to be important in ATR-dependent Chk1 phosphorylation. Here I describe the purification and characterization of checkpoint- and replication-related domains of human Claspin. I have identified a minimal functional domain of Claspin necessary and sufficient for activation of ATR dependent Chk1 phosphorylation in vitro. Claspin has also been shown to bind to DNA that mimics the structure of replication fork. I identified a minimal DNA binding domain in Claspin. It has also been suggested that Claspin interacts with replication fork proteins. To understand which replication fork proteins Claspin directly interacts with, I have purified the following replication fork factors: Rad17-RFC, polymerase epsilon, Timeless and Cdc45. I then mapped the regions of Claspin involved in each protein-protein interaction using in vitro immunoprecipitation assays. My results suggest that Claspin interacts with the aforementioned replication fork proteins and replication fork DNA. This work provides new insights into the replication and checkpoint functions of Claspin and reconstitution of a well-defined minimal in vitro checkpoint system

    Cryptochrome, Circadian Cycle, Cell Cycle Checkpoints, and Cancer

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    The mammalian circadian clock is a global regulatory system that controls many aspects of physiology, including behavior, metabolism, cell cycle progression, and overall fitness. CRYPTOCHROMES (CRYs) are core elements of the mammalian circadian clock, and loss of CRY expression leads to arrythmicity. Although much work has been done analyzing the mammalian clock, the molecular mechanisms underlying the clock and resulting from its disruption are still largely unknown. There is growing evidence that circadian rhythm disruption in both humans and rodents leads to predisposition to cancer and poor prognosis; however, it has not been determined if cancer predisposition is a hallmark of all types of clock disruption. Here I present evidence that arrhythmic Cry1-/-Cry2-/- mice possess an intact DNA damage checkpoint and repair system and are not predisposed to ionizing radiation-induced cancers relative to wild-type mice. In addition, experiments were conducted to determine the direct effect, if any, that CRY1 exerts on CLOCK-BMAL1 heterodimer DNA-binding. I find that CRY1 neither inhibits nor modifies the DNA binding of a heterodimer consisting of BMAL1 and a 342-amino acid fragment of CLOCK (CLOCK342) in vitro. However, this does not rule out the possibility that CRY1 could have an effect on a heterodimer of BMAL1 and full-length CLOCK in vitro

    Signal transduction mechanisms of cryptochrome

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    Photolyase and cryptochrome flavoproteins help living organisms manage the deleterious and beneficial effects of sunlight. Photolyase maintains genome integrity by reversing UV-induced DNA damage with near-UV/blue-light, and cryptochromes act as bluelight photosensory receptors to regulate growth in plants and entrainment of circadian rhythms in both plants and animals. Although photolyase and cryptochrome are highly structurally homologous and the photocycle of photolyase is known in great detail, we do not currently understand how cryptochromes signal in response to light. It is hypothesized that cryptochrome, like photolyase, employs light-driven electron transfer to initiate signaling, although the photocycle and other downstream signaling events remain to be described in detail. The studies described here were designed to take advantage of differences and similarities in the known functions of photolyases and cryptochromes in order to characterize the signaling mechanisms of cryptochromes. An examination of the structural and biochemical properties of plant and animal cryptochromes demonstrates that although they evolved independently from functionally distinct photolyase progenitors, they possess several unexpected similarities, demonstrating convergence in the evolution of cryptochromes. The implications of these results for the cryptochrome photocycle are discussed. Metazoan cryptochromes additionally have a critical, light-independent function in the molecular clock that engenders circadian rhythms. Other studies have shown that iv cryptochromes act as transcriptional repressors in the major transcription/translation feedback loop of the clock. I studied the interaction of mammalian cryptochromes with protein phosphatase 5 (PP5) and show that inhibition of PP5 by cryptochrome modulates the activity of the major clock kinase, casein kinase I epsilon. PP5 is required for proper cycling of the clock; therefore, these data provide the first demonstration of the role of a phosphatase in the mammalian circadian clock. Furthermore, they suggest that cryptochromes regulate the molecular clock by both transcriptional and posttranslational mechanisms
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