1,721,006 research outputs found
Investigating the role of H2A.X di-phosphorylation in the DNA Damage Response
Full text linkOne of the earliest responses to DNA double strand breaks is phosphorylation of the C-terminal tail of histone variant H2A.X at position S139. The phosphorylated form (?H2A.X) is a marker of DNA damage and promotes DNA damage repair (DDR). Recent work showed that H2A.X can also be phosphorylated at position Y142, and that increasing Y142 phosphorylation by siRNA knockdown of the Eyes Absent (Eya) phosphotyrosine phosphatases (which remove Y142 phosphates) leads to increased apoptosis in response to DNA damage. This led to the proposal that an epigenetic "switch" between mono-?H2A.X (S139 only phosphorylated) and di-?H2A.X (S139 and Y142 both phosphorylated) directs the choice between DNA repair vs apoptosis in response to DNA damage. In this study, we sought to test this "switch" hypothesis by testing for cooperativity between the DNA damaging drug, Bleomycin, and Benzbromarone - a pharmacological inhibitor of Eya phosphatases. Although little cooperativity between Bleomycin and Benzbromarone was found in cell proliferation assays, live-cell imaging with fluorescent markers of apoptosis showed an increase in cell death. Moreover, by using novel antibodies that specifically recognise the various phosphorylated forms of H2A.X, immunochemical staining revealed that di-?H2A.X is located adjacent to and "flanks" ?H2A.X in DDR foci, and is interspersed with ?H2A.X in apoptotic cells. Therefore, contrary to the "switch" hypothesis being the singular function of di-?H2A.X, these results suggest an additional model for the role of di-?H2A.X in DDR, in that it may also act as a limiting factor in the rate of expansion of ?H2A.X repair foci
Developing methods to detect and remedy DNA damage in sperm
Full text linkInfertility affects millions of couples worldwide, with male-related factors playing a significant role. While basic semen analysis is a standard method for evaluating male infertility, advanced sperm testing can enhance its accuracy. To gain insights into urologists' perspectives on advanced semen analysis tests, a survey was conducted among urologists from different geographical regions. The survey revealed a consensus on clinically relevant parameters in basic semen analysis. Among the various advanced sperm tests offered by urologists, sperm DNA damage testing was the most common. Challenges such as lack of familiarity, test availability, and cost were cited as reasons for not offering advanced testing. Analyzing the underlying causes of increased sperm DNA damage is crucial for guiding patient treatment. Oxidative stress is recognized as a significant contributor to sperm DNA damage, and assessing oxidative stress levels provides valuable information. Seminal oxidative stress can be assessed by determining oxidation-reduction potential (ORP) or reactive oxygen species (ROS) levels. High ORP and/or ROS levels were associated with poorer sperm parameters, and higher levels of sperm DNA damage. To address the need for cost-effective and readily available tests, an in-house flow cytometric sperm DNA damage testing service was validated. Data obtained from the validation of the acridine orange-based flow cytometric test (AOFT) demonstrated its reliability and consistency. Lifestyle modifications and innovative sperm preparation techniques, such as microfluidic-based sperm preparation, can help mitigate sperm DNA damage. Microfluidic devices enable the natural selection of sperm based on various parameters, and an investigative study has shown the microfluidic sperm separation device to produce comparable results to the gold standard method, density gradient centrifugation
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
Understanding the function of the transcriptional activator ZFY in relation to its structure and evolution
Full text linkThe Y chromosome is a small, gene-poor chromosome that is enriched with repetitive sequences. This is due to its inability to undergo recombination, which leads to genetic degeneration over evolutionary time. Consequently, it is sometimes regarded as a “functional wasteland”. The genes that persist on the Y chromosome are essential for sex determination and male germ cell development. Among these, the transcription factor ZFY is one of very few genes consistently present on the Y chromosome in almost all eutherian species, indicating that it must have essential functions in men. A further distinctive feature of ZFY is the presence of two distinct developmentally regulated splice variants; a ubiquitous full-length major variant and a testis-specific minor short variant. This thesis seeks to understand the evolution, structure and function of ZFY, building on recent theoretical advances in understanding the mechanisms of transcription factor activity, and on up-to-date transcriptomic and proteomic experimental techniques. This thesis comprises four results chapters that collectively probe different aspects of ZFY structure and function. First, a phylogenetic analysis defines conserved versus rapidly evolving regions of ZFY and relates this to newly predicted functional motifs within the acidic domain. Secondly, cross-species examination of ZFY splicing data reveals that the testis-specific splicing pattern predates its recruitment to the Y chromosome, and potentially implicates RBMY as a potential splicing factor involved. Thirdly, RNA-Seq analysis highlights the core downstream pathways regulated by each splice isoform of ZFY, and finally pull-down proteomics identifies a range of potential interacting partners. Overall, the results identify a potential novel feedback loop regulating ZFY splicing during testis development and suggest several key pathways that ZFY may regulate including WNT signalling, ErbB signalling and extracellular matrix remodelling. Whilst an earlier observation that the short ZFY form is mis-expressed in some cancers was replicated, a wider role for ZFY as a cancer-testis gene was generally not supported
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
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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