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Abstract 3674: The polyamine acetylation enzyme SAT1 drives mesenchymal features and therapeutic resistance in glioblastoma
No full textBackground:
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults. Characterization of GBM heterogeneity has identified four molecular subtypes based on transcriptomic profile: classical, neural, proneural and mesenchymal. Tumors harboring the mesenchymal gene signature are considered the most aggressive, invasive, and multitherapy-resistant. We identify the polyamine acetylation enzyme, SAT1 (spermidine/spermine N1-acetyltransferase 1) as a component of the mesenchymal gene signature and mesenchymal-associated gene sets including (1) Hallmark EMT and (2) Hallmark TNFa signaling via NF-κB.
Design/Methods:
To validate the role of SAT1 in driving mesenchymal features in vivo, we utilized a genetically flexible, CRISPR-based model of GBM. Tumor bearing mice were generated through in utero electroporation, resulting in ablation of PTEN, P53 and NF1 in developing cortical cells. SAT1 knockout was achieved through cloning of additional guide RNA’s against SAT1 into the tumor initiating plasmid.
Results:
In our model, we found increased levels of both SAT1 and acetylated polyamines in tumors compared to normal brain. Ablation of SAT1 was insufficient to prolong overall survival in mice but rendered the otherwise treatment resistant tumors highly sensitive to chemoRT. Bulk RNA sequencing of murine tumors revealed that SAT1 knockout resulted in reduced expression of the mesenchymal gene signature as well as genes implicated in EMT and TNFa/NFKb signaling.
Conclusions:
Collectively, these results reveal that SAT1 not only identifies mesenchymal GBM but also drives expression of the mesenchymal gene signature and mesenchymal features including multi-therapy resistance.
Citation Format: Ayush B. Rana, Timothy M. Horton, Vijay S. Thakur, Scott M. Welford. The polyamine acetylation enzyme SAT1 drives mesenchymal features and therapeutic resistance in glioblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3674
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
United States Foreign Intelligence Activities, Executive Order No. 12036, 43 FR 3674
No full textUnited States Foreign Intelligence Activities, Executive Order No. 12036, 43 FR 3674 ( Jan. 24, 1978)First page of documen
Kirby, Sarah Jane Jennie (Whalen), 1863-1918 (SC 3674)
No full textFinding aid and scan (Click on Additional Files below) for Manuscripts Small Collection 3674. Memoranda by Jennie Kirby, Warren County, Kentucky, of local deaths from 1899-1916. Using a blank Poll Book, she inscribes names, date of death, and in most cases the cause of death. African Americans and whites are included. Records of births, 1910-1911, are at the back of the book
Variations on the Author
No full text“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
No full textWe 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
No full textWe 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
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