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  1. Article ; Online: How chromosomal translocations arise to cause cancer: Gene proximity,

    Streb, Patrick / Kowarz, Eric / Benz, Tamara / Reis, Jennifer / Marschalek, Rolf

    iScience

    2023  Volume 26, Issue 6, Page(s) 106900

    Abstract: Chromosomal translocations (CTs) are a genetic hallmark of cancer. They could be identified as recurrent genetic aberrations in hemato-malignancies and solid tumors. More than 40% of all "cancer genes" were identified in recurrent CTs. Most of these CTs ... ...

    Abstract Chromosomal translocations (CTs) are a genetic hallmark of cancer. They could be identified as recurrent genetic aberrations in hemato-malignancies and solid tumors. More than 40% of all "cancer genes" were identified in recurrent CTs. Most of these CTs result in the production of oncofusion proteins of which many have been studied over the past decades. They influence signaling pathways and/or alter gene expression. However, a precise mechanism for how these CTs arise and occur in a nearly identical fashion in individuals remains to be elucidated. Here, we performed experiments that explain the onset of CTs: (1) proximity of genes able to produce prematurely terminated transcripts, which lead to the production of (2)
    Language English
    Publishing date 2023-05-19
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Vaccine-induced COVID-19 mimicry syndrome.

    Kowarz, Eric / Krutzke, Lea / Külp, Marius / Streb, Patrick / Larghero, Patrizia / Reis, Jennifer / Bracharz, Silvia / Engler, Tatjana / Kochanek, Stefan / Marschalek, Rolf

    eLife

    2022  Volume 11

    Abstract: To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 ... ...

    Abstract To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as a severe side effect occurring 4-14 days after the first vaccination and were often accompanied by thrombocytopenia. Besides CVST, splanchnic vein thromboses (SVT) and other thromboembolic events have been observed. These events only occurred following vaccination with adenoviral vector-based vaccines but not following vaccination with mRNA-based vaccines. Meanwhile, scientists have proposed an immune-based pathomechanism and the condition has been coined vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe an unexpected mechanism that could explain thromboembolic events occurring with DNA-based but not with RNA-based vaccines. We show that DNA-encoded mRNA coding for Spike protein can be spliced in a way that the transmembrane anchor of Spike is lost, so that nearly full-length Spike is secreted from cells. Secreted Spike variants could potentially initiate severe side effects when binding to cells via the ACE2 receptor. Avoiding such splicing events should become part of a rational vaccine design to increase safety of prospective vaccines.
    MeSH term(s) COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; ChAdOx1 nCoV-19/adverse effects ; Drug-Related Side Effects and Adverse Reactions/etiology ; Humans ; Pandemics ; SARS-CoV-2 ; Sinus Thrombosis, Intracranial/etiology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Syndrome ; Thrombocytopenia/etiology ; Vaccination/adverse effects ; Vaccines, DNA/adverse effects ; Venous Thrombosis/etiology
    Chemical Substances COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Vaccines, DNA ; spike protein, SARS-CoV-2 ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
    Language English
    Publishing date 2022-01-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.74974
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Diversification of the climatic niche drove the recent processes of speciation in Sigmodontinae (Rodentia, Cricetidae)

    Reis, Jennifer / Claudio J. Bidau / Renan Maestri / Pablo A. Martinez

    Mammal review. 2018 Oct., v. 48, no. 4

    2018  

    Abstract: Evolutionary radiations are among the most intriguing natural phenomena. Sigmodontine rodents form a megadiverse group for which doubts exist about the adaptive or non‐adaptive nature of its radiation. We analysed whether or not the rates of ... ...

    Abstract Evolutionary radiations are among the most intriguing natural phenomena. Sigmodontine rodents form a megadiverse group for which doubts exist about the adaptive or non‐adaptive nature of its radiation. We analysed whether or not the rates of diversification of species of Sigmodontinae are related to the rates of diversification of the climatic niches occupied by the species. Our results show a clear association between niche diversification and speciation processes. However, this association is linked to recent and independent processes of diversification in sigmodontines, as opposed to an early link that would indicate a niche‐filling consistent with an adaptive radiation of the subfamily.
    Keywords Sigmodontinae ; adaptive radiation ; niches ; rodents
    Language English
    Dates of publication 2018-10
    Size p. 328-332.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 2020637-9
    ISSN 1365-2907 ; 0305-1838
    ISSN (online) 1365-2907
    ISSN 0305-1838
    DOI 10.1111/mam.12128
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Generation of a Sleeping Beauty Transposon-Based Cellular System for Rapid and Sensitive Screening for Compounds and Cellular Factors Limiting SARS-CoV-2 Replication.

    Widera, Marek / Wilhelm, Alexander / Toptan, Tuna / Raffel, Johanna M / Kowarz, Eric / Roesmann, Fabian / Grözinger, Finn / Siemund, Anna Lena / Luciano, Vanessa / Külp, Marius / Reis, Jennifer / Bracharz, Silvia / Pallas, Christiane / Ciesek, Sandra / Marschalek, Rolf

    Frontiers in microbiology

    2021  Volume 12, Page(s) 701198

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 infectivity in cell culture are so far time-consuming and labor-intensive. Using the Sleeping Beauty transposase system, we generated a robust and versatile cellular infection model that allows SARS-CoV-2 infection experiments compatible for high-throughput and live cell imaging. The model is based on lung derived A549 cells, which show a profound interferon response and convenient cell culture characteristics. ACE2 and TMPRSS2 were introduced for constitutive expression (A549-AT). Subclones with varying levels of ACE2/TMPRSS2 were screened for optimal SARS-CoV-2 susceptibility. Furthermore, extensive evaluation demonstrated that SARS-CoV-2 infected A549-AT cells were distinguishable from mock-infected cells and already showed approximately 12 h post infection a clear signal to noise ratio in terms of cell roughness, fluorescence and a profound visible cytopathic effect. Moreover, due to the high transfection efficiency and proliferation capacity, Sleeping Beauty transposase-based overexpression cell lines with a second inducible fluorescence reporter cassette (eGFP) can be generated in a very short time, enabling the investigation of host and restriction factors in a doxycycline-inducible manner. Thus, the novel model cell line allows rapid and sensitive monitoring of SARS-CoV-2 infection and the screening for host factors essential for viral replication.
    Language English
    Publishing date 2021-07-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.701198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Generation of a Sleeping Beauty transposon-based cellular system for rapid and sensitive identification of SARS-CoV-2 host dependency and restriction factors

    Widera, Marek / Wilhelm, Alexander / Toptan, Tuna / Raffel, Johanna M / Kowarz, Eric / Roesmann, Fabian / Siemund, Anna Lena / Luciano, Vanessa / Kuelp, Marius / Reis, Jennifer / Bracharz, Silvia / Pallas, Christiane / Ciesek, Sandra / Marschalek, Rolf

    bioRxiv

    Abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 ... ...

    Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 infectivity in cell culture are so far time-consuming and labor-intensive. Using the Sleeping Beauty transposase system, we generated a robust and versatile reporter cell system that allows SARS-CoV-2 infection experiments compatible for high-throughput and live cell imaging. The reporter cell is based on lung derived A549 cells, which show a profound interferon response and convenient cell culture characteristics. ACE2 and TMPRSS2 were introduced for constitutive expression in A549 cells. Subclones with varying levels of ACE2/TMPRSS2 were screened for optimal SARS-CoV2 susceptibility. Furthermore, extensive evaluation demonstrated that SARS-CoV-2 infected reporter cells were distinguishable from mock-infected cells and already showed approximately 12 h post infection a clear signal to noise ratio in terms of cell roughness, fluorescence and a profound visible cytopathic effect. Moreover, due to the high transfection efficiency and proliferation capacity, Sleeping Beauty transposase-based overexpression cell lines with a second inducible fluorescence reporter cassette (eGFP) can be generated in a very short time, enabling the investigation of host and restriction factors in a doxycycline-inducible manner. Thus, the novel reporter cell line allows rapid and sensitive detection of SARS-CoV-2 infection and the screening for host factors essential for viral replication.
    Keywords covid19
    Language English
    Publishing date 2021-04-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.04.27.441606
    Database COVID19

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