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  1. Article ; Online: Retrospective analysis of a STEM outreach event reveals positive influences on student attitudes toward STEM careers but not scientific methodology.

    Crawford, A J / Hays, Cassandra L / Schlichte, Sarah L / Greer, Sydney E / Mallard, Halle J / Singh, Ryan M / Clarke, Martina A / Schiller, Alicia M

    Advances in physiology education

    2021  Volume 45, Issue 3, Page(s) 427–436

    Abstract: Substantial, involved, and expensive efforts to promote the dissemination of scientific knowledge and career interest in Science, Technology, Engineering, and Mathematics (STEM) are enthusiastically supported by many scientific, federal, and local ... ...

    Abstract Substantial, involved, and expensive efforts to promote the dissemination of scientific knowledge and career interest in Science, Technology, Engineering, and Mathematics (STEM) are enthusiastically supported by many scientific, federal, and local organizations. The articulated underlying goals for these efforts include an enhanced public understanding of science and science-related policy, an increased diversity in STEM careers, and an increase in the future STEM workforce. This effort is primarily driven by an underperformance of the United States that includes poor test performance and limited number of students pursuing STEM degrees. Despite this investment, attitudes toward STEM have not notably changed. The goal of this project was to determine students' attitudes toward STEM in response to a previously established scientific outreach event. This event was used to address three common goals in STEM outreach: STEM literacy, diversity and inclusion, and career preparedness. We found there was a notable difference in the attitudes toward scientific activities and interest in pursuing a "Science Career" after participation in this event. Strikingly, interest in hypothesis development, the keystone of all STEM disciplines, was the least liked of all the activities offered during the event. Our data suggest that events designed to enhance interest in pursuing a STEM career may benefit from different elements compared with events designed to increase understanding of STEM literacy concepts, such as hypothesis development.
    MeSH term(s) Attitude ; Career Choice ; Humans ; Mathematics ; Retrospective Studies ; Students ; Technology
    Language English
    Publishing date 2021-06-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1024917-5
    ISSN 1522-1229 ; 1043-4046
    ISSN (online) 1522-1229
    ISSN 1043-4046
    DOI 10.1152/advan.00118.2020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma.

    Mallard, Halle J / Wan, Shibiao / Nidhi, Prakriti / Hanscom-Trofy, Yvan D / Mohapatra, Bhopal / Woods, Nicholas T / Lopez-Guerrero, Jose Antonio / Llombart-Bosch, Antonio / Machado, Isidro / Scotlandi, Katia / Kreiling, Natasha F / Perry, Megan C / Mirza, Sameer / Coulter, Donald W / Band, Vimla / Band, Hamid / Ghosal, Gargi

    Molecular cancer research : MCR

    2023  Volume 21, Issue 11, Page(s) 1186–1204

    Abstract: In this study, we identify USP1 as a transcriptional target of EWS::FLI1 and demonstrate the requisite function of USP1 in Ewing sarcoma (EWS) cell survival in response to endogenous replication stress. EWS::FLI1 oncogenic transcription factor drives ... ...

    Abstract In this study, we identify USP1 as a transcriptional target of EWS::FLI1 and demonstrate the requisite function of USP1 in Ewing sarcoma (EWS) cell survival in response to endogenous replication stress. EWS::FLI1 oncogenic transcription factor drives most EWS, a pediatric bone cancer. EWS cells display elevated levels of R-loops and replication stress. The mechanism by which EWS cells override activation of apoptosis or cellular senescence in response to increased replication stress is not known. We show that USP1 is overexpressed in EWS and EWS::FLI1 regulates USP1 transcript levels. USP1 knockdown or inhibition arrests EWS cell growth and induces cell death by apoptosis. Mechanistically, USP1 regulates Survivin (BIRC5/API4) protein stability and the activation of caspase-9 and caspase-3/7 in response to endogenous replication stress. Notably, USP1 inhibition sensitizes cells to doxorubicin and etoposide treatment. Together, our study demonstrates that USP1 is regulated by EWS::FLI1, the USP1-Survivin axis promotes EWS cell survival, and USP1 inhibition sensitizes cells to standard of care chemotherapy.
    Implications: High USP1 and replication stress levels driven by EWS::FLI1 transcription factor in EWS are vulnerabilities that can be exploited to improve existing treatment avenues and overcome drug resistance.
    MeSH term(s) Humans ; Child ; Sarcoma, Ewing/metabolism ; Proto-Oncogene Protein c-fli-1/genetics ; Proto-Oncogene Protein c-fli-1/metabolism ; Survivin/genetics ; Survivin/metabolism ; RNA-Binding Protein EWS/genetics ; RNA-Binding Protein EWS/metabolism ; Cell Line, Tumor ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Gene Expression Regulation, Neoplastic ; Ubiquitin-Specific Proteases/metabolism
    Chemical Substances Proto-Oncogene Protein c-fli-1 ; Survivin ; RNA-Binding Protein EWS ; Oncogene Proteins, Fusion ; USP1 protein, human (EC 3.4.19.12) ; Ubiquitin-Specific Proteases (EC 3.4.19.12)
    Language English
    Publishing date 2023-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-23-0323
    Database MEDical Literature Analysis and Retrieval System OnLINE

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