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  1. AU="Amrhein, Carolin"
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  3. AU="Bell, T J"
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  1. Article: Genomics Integrated Systems Transgenesis (GENISYST) for gain-of-function disease modelling in Göttingen Minipigs

    Maxeiner, Joachim / Sharma, Rahul / Amrhein, Carolin / Gervais, Frederic / Duda, Maria / Ward, Jonathan / Mikkelsen, Lars Friis / Forster, Roy / Malewicz, Michal / Krishnan, Jaya

    Journal of pharmacological and toxicological methods. 2021 Mar., Apr., v. 108

    2021  

    Abstract: Göttingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Göttingen ... ...

    Abstract Göttingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Göttingen Minipigs models has increased, as advanced genetic techniques simplify the generation of animals with precisely tailored modifications. These modifications are designed to replicate genetic alterations responsible for human disease. In addition to serving as valuable large animal disease models, transgenic Göttingen Minipigs are also considered promising donors for xenotransplantation. Current technologies for generation of transgenic minipigs demand a long development and production time of typically 2–3 years. To overcome this limitation and expand the use of Göttingen Minipigs for disease modelling and drug testing, we developed the GENISYST (Genomics Integrated Systems Transgenesis) technology platform for rapid and efficient generation of minipigs based transgenic disease models. As proof of concept, we report the successful generation of transgenic minipigs expressing green fluorescent protein (GFP) in multiple disease-relevant tissues including liver, heart, kidney, lungs, and the central nervous system (CNS). Our data demonstrates the feasibility, efficiency, and utility of GENISYST for rapid one-step generation of transgenic minipigs for human disease modelling in drug discovery and development.
    Keywords animal diseases ; central nervous system ; drugs ; gain-of-function mutation ; genetically modified organisms ; genomics ; green fluorescent protein ; heart ; human diseases ; kidneys ; liver ; miniature swine ; toxicology ; transgenesis ; xenotransplantation
    Language English
    Dates of publication 2021-03
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1105919-9
    ISSN 1873-488X ; 1056-8719
    ISSN (online) 1873-488X
    ISSN 1056-8719
    DOI 10.1016/j.vascn.2021.106956
    Database NAL-Catalogue (AGRICOLA)

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    Zs.A 1440: Show issues Location:
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  2. Article ; Online: Genomics Integrated Systems Transgenesis (GENISYST) for gain-of-function disease modelling in Göttingen Minipigs.

    Maxeiner, Joachim / Sharma, Rahul / Amrhein, Carolin / Gervais, Frederic / Duda, Maria / Ward, Jonathan / Mikkelsen, Lars Friis / Forster, Roy / Malewicz, Michal / Krishnan, Jaya

    Journal of pharmacological and toxicological methods

    2021  Volume 108, Page(s) 106956

    Abstract: Göttingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Göttingen ... ...

    Abstract Göttingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Göttingen Minipigs models has increased, as advanced genetic techniques simplify the generation of animals with precisely tailored modifications. These modifications are designed to replicate genetic alterations responsible for human disease. In addition to serving as valuable large animal disease models, transgenic Göttingen Minipigs are also considered promising donors for xenotransplantation. Current technologies for generation of transgenic minipigs demand a long development and production time of typically 2-3 years. To overcome this limitation and expand the use of Göttingen Minipigs for disease modelling and drug testing, we developed the GENISYST (Genomics Integrated Systems Transgenesis) technology platform for rapid and efficient generation of minipigs based transgenic disease models. As proof of concept, we report the successful generation of transgenic minipigs expressing green fluorescent protein (GFP) in multiple disease-relevant tissues including liver, heart, kidney, lungs, and the central nervous system (CNS). Our data demonstrates the feasibility, efficiency, and utility of GENISYST for rapid one-step generation of transgenic minipigs for human disease modelling in drug discovery and development.
    MeSH term(s) Animals ; Disease Models, Animal ; Gain of Function Mutation ; Gene Transfer Techniques ; Genomics ; Humans ; Swine/genetics ; Swine, Miniature
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1105919-9
    ISSN 1873-488X ; 1056-8719
    ISSN (online) 1873-488X
    ISSN 1056-8719
    DOI 10.1016/j.vascn.2021.106956
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

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  3. Article ; Online: Amyloid-β (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study.

    Stamatelopoulos, Kimon / Mueller-Hennessen, Matthias / Georgiopoulos, Georgios / Sachse, Marco / Boeddinghaus, Jasper / Sopova, Kateryna / Gatsiou, Aikaterini / Amrhein, Carolin / Biener, Moritz / Vafaie, Mehrshad / Athanasouli, Fani / Stakos, Dimitrios / Pateras, Konstantinos / Twerenbold, Raphael / Badertscher, Patrick / Nestelberger, Thomas / Dimmeler, Stefanie / Katus, Hugo A / Zeiher, Andreas M /
    Mueller, Christian / Giannitsis, Evangelos / Stellos, Konstantinos

    Annals of internal medicine

    2018  Volume 168, Issue 12, Page(s) 855–865

    Abstract: Background: Amyloid-β (1-40) (Aβ40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease.: Objective: To determine the prognostic and reclassification value of baseline ... ...

    Abstract Background: Amyloid-β (1-40) (Aβ40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease.
    Objective: To determine the prognostic and reclassification value of baseline circulating levels of Aβ40 after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
    Design: Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734).
    Setting: Academic hospitals in 7 European countries.
    Participants: Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively.
    Measurements: All-cause mortality was the primary end point.
    Results: Amyloid-β (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid-β (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05).
    Limitation: At low concentrations of Aβ40, dose-response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure Aβ40.
    Conclusion: Circulating Aβ40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of Aβ40 as a novel biomarker in NSTE-ACS should be further explored and validated.
    Primary funding source: German Cardiac Society.
    MeSH term(s) Acute Coronary Syndrome/blood ; Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/mortality ; Aged ; Amyloid beta-Peptides/blood ; Biomarkers/blood ; Female ; Humans ; Male ; Peptide Fragments/blood ; Prognosis ; Retrospective Studies ; Risk Factors
    Chemical Substances Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; amyloid beta-protein (1-40)
    Language English
    Publishing date 2018-05-22
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 336-0
    ISSN 1539-3704 ; 0003-4819
    ISSN (online) 1539-3704
    ISSN 0003-4819
    DOI 10.7326/M17-1540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ua VI Zs.178/2: Show issues Location:
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  4. Article ; Online: Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.

    Stellos, Konstantinos / Gatsiou, Aikaterini / Stamatelopoulos, Kimon / Perisic Matic, Ljubica / John, David / Lunella, Federica Francesca / Jaé, Nicolas / Rossbach, Oliver / Amrhein, Carolin / Sigala, Frangiska / Boon, Reinier A / Fürtig, Boris / Manavski, Yosif / You, Xintian / Uchida, Shizuka / Keller, Till / Boeckel, Jes-Niels / Franco-Cereceda, Anders / Maegdefessel, Lars /
    Chen, Wei / Schwalbe, Harald / Bindereif, Albrecht / Eriksson, Per / Hedin, Ulf / Zeiher, Andreas M / Dimmeler, Stefanie

    Nature medicine

    2016  Volume 22, Issue 10, Page(s) 1140–1150

    Abstract: Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease ...

    Abstract Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx
    MeSH term(s) 3' Untranslated Regions ; Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adult ; Aged ; Aged, 80 and over ; Aortic Aneurysm/genetics ; Atherosclerosis/genetics ; Carotid Artery Diseases/genetics ; Cathepsins/genetics ; Coronary Artery Disease/genetics ; ELAV-Like Protein 1/genetics ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Gene Knock-In Techniques ; Gene Knockdown Techniques ; High-Throughput Nucleotide Sequencing ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia/genetics ; Immunoblotting ; Inosine/metabolism ; Interferon-gamma/pharmacology ; Male ; Middle Aged ; RNA Editing/drug effects ; RNA Editing/genetics ; RNA Processing, Post-Transcriptional/drug effects ; RNA Processing, Post-Transcriptional/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Tumor Necrosis Factor-alpha/pharmacology
    Chemical Substances 3' Untranslated Regions ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; RNA, Messenger ; RNA-Binding Proteins ; Tumor Necrosis Factor-alpha ; Inosine (5A614L51CT) ; Interferon-gamma (82115-62-6) ; Cathepsins (EC 3.4.-) ; cathepsin S (EC 3.4.22.27) ; ADAR protein, human (EC 3.5.4.37) ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2016-09-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm.4172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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