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Abstract 4790: Oxidation in the nucleotide pool as a novel targetable vulnerability in pancreatic ductal adenocarcinoma
No full textAbstract Oncogenic RAS signaling is mediated by reactive oxygen species (ROS) signaling. However, oncogenic ROS also evoke tumor suppressive damage, necessitating adaptive redox protective mechanisms. We previously reported that MTH1, the main mammalian 8-oxodGTPase, comprises one such critical adaptation. High MTH1 expression significantly correlates with poor disease-free survival in several KRAS-driven tumors. We have shown in RAS-driven xenograft cancer models that MTH1 is critical for the maintenance of ROS-driven signaling and prevention of DNA damage-induced senescence. However, how MTH1 loss affects KRAS-driven spontaneous tumor formation is unknown. We focused on pancreatic ductal adenocarcinoma (PDAC) due to the high prevalence of driving oncogenic KRASG12D mutations, and the lack of MTH1 studies. Therefore, we depleted MTH1 via shRNA in MIA PacCa-2 and SU.86.86 cell lines and generated novel MTH1-null Pdx1Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC), Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) and corresponding MTH1-wildtype strains. We found MTH1 knockdown significantly reduced growth of KRAS-driven PDAC cells, and that germline MTH1 deficiency reduced tumor burden in the short latency PKT but not the long latency KPC animals. The PKT tumors exhibited higher overall 8-oxodGTPase activity and reduced total 8-oxo-dGTPase activity in the MTH1-deficient background, unlike KPC tumors. This finding suggests that in aggressive KRAS-driven tumors, redundant 8-oxodGTPase activity cannot compensate for MTH1 loss to prevent oncogenic stress-induced tumor suppression. Additionally, both MTH1-depleted PDAC cell lines and the smaller MTH1-null PKT tumors had decreased EGFR expression, suggesting MTH1 loss compromises this ROS-driven pathway. RNA-seq analysis revealed MTH1 deficiency altered MDSC gene expression in the PKT model, suggesting better anti-tumor response through improved immune infiltration in a typically immunologically cold tumor. Our results indicate MTH1 targeting could benefit aggressive PDAC stages. We further show PDAC tumors possess redundancy in MTH1 8-oxodGTPase function, which needs to be better understood in order to therapeutically leverage current MTH1 inhibitors, which do not target this redundancy. Citation Format: Beatriz Mateo-Victoriano, Ling Zhang, Govindi J. Samaranayake, Cassie Due, Clara Troccoli, Julia Zaias, Nagaraj Nagathihalli, Michael VanSaun, Michael G. Mohsen, Eric T. Kool, Priyamvada Rai. Oxidation in the nucleotide pool as a novel targetable vulnerability in pancreatic ductal adenocarcinoma. [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 4790
Linked collectors and determiners for: Revision of the genus Allometopon Kertész (Diptera: Clusiidae).
No full textNatural history specimen data linked to collectors and determiners held within, "Revision of the genus Allometopon Kertész (Diptera: Clusiidae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/db12a9b2-ae53-4790-bdba-6a5799762618">https://bionomia.net/dataset/db12a9b2-ae53-4790-bdba-6a5799762618</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/db12a9b2-ae53-4790-bdba-6a5799762618">https://gbif.org/dataset/db12a9b2-ae53-4790-bdba-6a5799762618</a>. Formatted as a Frictionless Data package
Greenhouse Gas Emissions in Rosemount: Analysis and Recommendations
No full textPresentation and memo (report) completed by students enrolled in PA 4790/5790: Sustainable Infrastructure and Cities, taught by Anu Ramaswami in spring 2015.This project was completed as part of a year-long partnership between the City of Rosemount and the University of Minnesota’s Resilient Communities Project (http://www.rcp.umn.edu). The City of Rosemount is actively working to minimize its contribution to climate change by reducing greenhouse gas emissions. The goal of this project was to develop a climate action plan for the City of Rosemount that identifies specific strategies for reducing greenhouse gas emissions throughout the community. In collaboration with city project lead Jason Lindahl, a planner for the City of Rosemount, a team of students in PA 4790/5790: Sustainable Infrastructure and Cities analyzed local data and developed recommendations to reduce carbon emissions in the City of Rosemount for the energy, transportation, water, and food sectors, in addition to general recommendations. A final presentation and memo to the City of Rosemount from the project are available.This project was supported by the Resilient Communities Project (RCP), a program at the University of Minnesota that convenes the wide-ranging expertise of U of M faculty and students to address strategic local projects that advance community resilience and sustainability. RCP is a program of the Center for Urban and Regional Affairs (CURA). More information at http://www.rcp.umn.eduStudents enrolled in PA 4790/5790. (2015). Greenhouse Gas Emissions in Rosemount: Analysis and Recommendations. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/180463
Linked collectors and determiners for: University of Cincinnati, Margaret H. Fulford Herbarium - Bryophytes.
No full textNatural history specimen data linked to collectors and determiners held within, "University of Cincinnati, Margaret H. Fulford Herbarium - Bryophytes". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/6cfce8da-c177-4790-b038-1202dd33e9d7">https://bionomia.net/dataset/6cfce8da-c177-4790-b038-1202dd33e9d7</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/6cfce8da-c177-4790-b038-1202dd33e9d7">https://gbif.org/dataset/6cfce8da-c177-4790-b038-1202dd33e9d7</a>. Formatted as a Frictionless Data package
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
House at 4790 S. Cherry Street built in the early 1890s
No full textHouse at 4790 S.Cherry St. George William Healy built this home and brought his bride Janet Johnson Pender here in 1899; later occupants were Brandon Johnson, Clarks, & Andersons
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
Combining Everolimus and Ku0063794 Promotes Apoptosis of Hepatocellular Carcinoma Cells via Reduced Autophagy Resulting from Diminished Expression of miR-4790-3p
No full textIt is challenging to overcome the low response rate of everolimus in the treatment of patients with hepatocellular carcinoma (HCC). To overcome this challenge, we combined everolimus with Ku0063794, the inhibitor of mTORC1 and mTORC2, to achieve higher anticancer effects. However, the precise mechanism for the synergistic effects is not clearly understood yet. To achieve this aim, the miRNAs were selected that showed the most significant variation in expression according to the mono- and combination therapy of everolimus and Ku0063794. Subsequently, the roles of specific miRNAs were determined in the processes of the treatment modalities. Compared to individual monotherapies, the combination therapy significantly reduced viability, increased apoptosis, and reduced autophagy in HepG2 cells. The combination therapy led to significantly lower expression of miR-4790-3p and higher expression of zinc finger protein225 (ZNF225)—the predicted target of miR-4790-3p. The functional study of miR-4790-3p and ZNF225 revealed that regarding autophagy, miR-4790-3p promoted it, while ZNF225 inhibited it. In addition, regarding apoptosis, miR-4790-3p inhibited it, while ZNF225 promoted it. It was also found that HCC tissues were characterized by higher expression of miR-4790-3p and lower expression of ZNF225; HCC tissues were also characterized by higher autophagic flux. We, thus, conclude that the potentiated anticancer effect of the everolimus and Ku0063794 combination therapy is strongly associated with reduced autophagy resulting from diminished expression of miR-4790-3p, as well as higher expression of ZNF225
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