1,720,957 research outputs found
Analysis of CENP-A loading and misincorporation in Drosophila melanogaster
Get PDFCentromeric Protein-A (CENP-A, known as Centromere Identifier (CID) in Drosophila
melanogaster) is an epigenetic marker for centromere identity and propagation (Allshire &
Karpen, 2008). Upon elevated expression, CENP-A mislocalizes to ectopic sites and can give
rise to neocentromeres, thereby leading to genome instability (Heun et al., 2006; Shrestha
et al., 2017; Tomonaga, Matsushita, Yamaguchi, et al., 2003). Promiscuously-incorporated
CENP-A is a prognostic and predictive marker for tumor progression (Filipescu et al., 2017).
To gain further understanding on this mechanism of mislocalization, I explored alternative
CENP-A incorporation and elimination pathways, using cultured fly S2 cells and adult flies.
Previous studies suggested that component of general assembly factors RbAp48 is involved
in CENP-A ectopic incorporation (Furuyama, Dalal, & Henikoff, 2006; Spiller-Becker,
unpublished) and de novo deposition in multiple eukaryotic lineages (Fujita et al., 2007;
Hayashi et al., 2004; Lee et al., 2016). RbAp48 is found in several chromatin assembly,
remodelling, and modification complexes (Doyen et al., 2013; Rai et al., 2013), but it is yet
unknown whether RbAp48 carries out this function together with a multi-subunit complex.
RbAp48 is a subunit of Chromatin Assembly Factor-1 (CAF-1) complex (Tyler et al., 1996).
Thus, I first tested the role of CAF-1 in CID mislocalization but did not find convincing
evidence for an involvement of CAF-1 in CID ectopic loading. Levels of ectopically expressed
and misincorporated CID were stable upon CAF-1 depletion and no physical interaction was
detected. Hence, I decided to search for the role of other potential RbAp48-containing
complexes in CID misincorporation, using a Crosslinked Immunoprecipitation Mass Spec
(Xlink-IP-MS) approach. Interestingly, I identified a dual catalytic and RbAp48-containing
multi-subunit complex so called Nucleosome Remodelling and Deacetylase (NuRD) complex.
NuRD has two catalytic functions, namely nucleosome remodelling and histone
deacetylation (Denslow & Wade, 2007). I detected a physical interaction of overexpressed
CID with the NuRD complex core components Mi-2, MTA1-like and RbAp48 and
misexpressed CID protein levels decreased and chromatin incorporation upon depletion of
the catalytic component Mi-2 and MTA1-like scaffold protein. Moreover, upon disruption of
the RbAp48 interaction surface with MTA1-like, the nuclear transport and misincorporation
of CID were impaired. Taken together, these results suggest that RbAp48/MTA1-like binding
is required for nuclear incorporation of overexpressed CID, and catalytic and scaffold
components of the NuRD complex are essential for the mislocalization of CID. Xlink-IP-MS
also detected hyperplastic discs (hyd), an E3 ubiquitin ligase (Moncrieff et al., 2015) as CID
interacting component. Mislocalized CENP-A is known to be targeted by E3 ligases in several
eukaryotes (Hewawasam et al., 2010; Moreno-Moreno et al., 2011; Ranjitkar et al., 2010).
Thus, I also tested the hypothesis that CID is targeted by hyd for proteasomal degradation.
The genetic and physical interaction between CID and hyd were determined. Hyd
overexpression resulted in poly-ubiquitination and destabilization of CID. Endogenous and
ectopically expressed CID protein levels were found to increase upon hyd depletion.
Collectively, these results demonstrated that hyd E3 ligase regulates CID protein levels
through ubiquitin-mediated proteolysis. In summary, I found that the NuRD complex plays
an essential role in nuclear localization and misincorporation of misexpressed CID, and its
stability and incorporation are controlled by hyd E3 ligase. The findings presented in this
work may contribute to our understanding of misregulated CENP-A in cancer and new
strategies for tackling the detrimental misincorporation in many different tumor entities
Role of JMJD5 in liver cancer
No full textCataloged from PDF version of article.Includes bibliographical references leaves 90-94.Being one of the most common cancer types in human population, hepatocellular
carcinoma (HCC) has high rate of deaths due to the challenges in its diagnosis and
treatment. In recent years, epigenetic regulators have come into play in HCC
research to overcome with those challenges. As potential drug targets, histone
demethylases has drawn a lot of interest. In this respect, several studies have focused
on a specific member of this family, JMJD5, suggesting its possible function in
tumor suppression, while the opposite argument has also been proposed by several
reports. Preceding studies on JMJD5 in our lab also pointed to a possible tumor
suppressor function. Hence, this study aimed to elucidate the role of JMJD5 in liver
cancer development using SNU449 HCC cell line stably expressing JMJD5. For this
purpose, stable clones overexpressing wild-type and mutant JMJD5 as well as
controls were generated. A comparative analysis of these clones was performed. No
definite results could be obtained for the effect of JMJD5 on cell proliferation, but
the number of cells in G1 declined, whereas that in G2/M inclined in clones
expressing wild-type and mutant JMJD5, suggesting that JMJD5 affects cell cycle
progression. In addition, cell motility was decreased, while anchorage-independent
colony formation ability was enhanced in both mutant and wild type JMJD5-
expressing clones. Decrease in cell motility is considered to be anti-tumoral, whereas
anchorage-independent growth is a malignant change. Our findings suggest that
JMJD5 may have a quite complex role in liver tumorigenesis. Further in vivo studies
may help to clarify some of these apparently conflicting in vitro effects.Demirdizen, Engi
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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