1,721,098 research outputs found
Abstract LB-110: Comparison of the effects of tubulin-targeting and DNA-damaging agents on the modulation and distribution of HSP90, pHSP90αT5/7, and tubulin in cancer cells
No full textAbstract
Microtubules (MTs) are essential architectural components of cells whose dynamic structures are critical for multiple functions including cell division, intracellular signaling, and trafficking. Many proteins are associated with MTs or their motors, including molecular chaperones such as heat shock protein 90 (HSP90), a key component of the cellular proteostatic machinery. The coordinated interplay of these processes is crucial for maintaining normal or malignant cell phenotypes. Alterations in protein levels, their localization and/or post-translational modifications (PTMs), such as phosphorylation or acetylation, are recognized as targets for disruption and may impact cell viability. To that end, we investigated the levels of HSP90 and pHSP90αT5/7 (a unique PTM previously associated with DNA damage) in both prostate (22RV1, PC3), and colorectal (HCT116wt, HCT116 DNA-PK -/-) carcinoma cell lines after treatment with microtubule-targeting agents (MTAs) or DNA-damaging agents (DDAs). We observed a dose dependent increase in the level of pHSP90αT5/7 protein in each of the cell lines treated with an MTA (paclitaxel (PTX), vincristine) or a DDA (gemcitabine, oxaliplatin) compared to the untreated control, whereas the levels of HSP90 remained monotonous throughout. The increases in pHSP90αT5/7 were independent of DNA-PK status for the HCT116 cells. These observations were accompanied by increasing levels of γ-H2AX and acetylated tubulin, the latter prominent following treatment with PTX. When cell lysates were separated into cytoplasmic (C) and nuclear (N) fractions, HSP90 and pHSP90αT5/7 were located predominantly in the C fractions while acetylated tubulin was surprisingly distributed between the C and N fractions as was γ-H2AX. Markers of cytoplasmic localization, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the voltage-dependent anion channel (VDAC), and of nuclear localization, including phospho-Histone H3 and acetylated-Histone H3, were each segregated to their appropriate cellular compartments. HSP90α was previously shown to be a substrate and chaperone of the nuclear kinase DNA-PK and its DNA-PK dependent phosphorylation in the nucleus at T5 and T7 was necessary for the apoptotic response to TRAIL (Solier S, et al PNAS, 105:32, 2012). In contrast, our data demonstrate that HSP90αT5/7 phosphorylation also occurs in response to MTA, but is localized in cytosol and is independent of DNA-PK. Meanwhile, others have reported that tubulin acetylation favors HSP90 recruitment to MTs, stimulating the signaling function of HSP90 clients (Giustiniani, J, et al Cell Sig, 21, 2009). The unique effects of MTAs and DDAs on pHSP90αT5/7 and tubulin acetylation have implications for malignant cell survival and drug resistance mechanisms. Experiments are underway to determine the significance of cytosolic pHsp90αT5/7 and nuclear acetylated tubulin in these cellular tumor models.
Citation Format: Marianne S. Poruchynsky, Michael Moses, Len Neckers. Comparison of the effects of tubulin-targeting and DNA-damaging agents on the modulation and distribution of HSP90, pHSP90αT5/7, and tubulin in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-110. doi:10.1158/1538-7445.AM2017-LB-110</jats:p
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
- …
