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  1. Article ; Online: Genetic duplication of tissue factor reveals subfunctionalization in venous and arterial hemostasis.

    Grzegorski, Steven J / Zhao, Yakun / Richter, Catherine E / Ku, Chia-Jui / Lavik, Kari I / Paul, Divyani / Morrissey, James H / Shavit, Jordan A

    PLoS genetics

    2022  Volume 18, Issue 11, Page(s) e1010534

    Abstract: Tissue factor (TF) is an evolutionarily conserved protein necessary for initiation of hemostasis. Zebrafish have two copies of the tissue factor gene (f3a and f3b) as the result of an ancestral teleost fish duplication event (so called ohnologs). In vivo ...

    Abstract Tissue factor (TF) is an evolutionarily conserved protein necessary for initiation of hemostasis. Zebrafish have two copies of the tissue factor gene (f3a and f3b) as the result of an ancestral teleost fish duplication event (so called ohnologs). In vivo physiologic studies of TF function have been difficult given early lethality of TF knockout in the mouse. We used genome editing to produce knockouts of both f3a and f3b in zebrafish. Since ohnologs arose through sub- or neofunctionalization, they can unmask unknown functions of non-teleost genes and could reveal whether mammalian TF has developmental functions distinct from coagulation. Here we show that a single copy of either f3a or f3b is necessary and sufficient for normal lifespan. Complete loss of TF results in lethal hemorrhage by 2-4 months despite normal embryonic and vascular development. Larval vascular endothelial injury reveals predominant roles for TFa in venous circulation and TFb in arterial circulation. Finally, we demonstrate that loss of TF predisposes to a stress-induced cardiac tamponade independent of its role in fibrin formation. Overall, our data suggest partial subfunctionalization of TFa and TFb. This multigenic zebrafish model has the potential to facilitate study of the role of TF in different vascular beds.
    MeSH term(s) Animals ; Mice ; Gene Duplication ; Larva ; Thromboplastin/genetics ; Thromboplastin/physiology ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/genetics ; Hemostasis/genetics ; Veins/physiology ; Arteries/physiology
    Chemical Substances Thromboplastin (9035-58-9) ; Zebrafish Proteins
    Language English
    Publishing date 2022-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1010534
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Loss of fibrinogen in zebrafish results in an asymptomatic embryonic hemostatic defect and synthetic lethality with thrombocytopenia.

    Hu, Zhilian / Lavik, Kari I / Liu, Yang / Vo, Andy H / Richter, Catherine E / Di Paola, Jorge / Shavit, Jordan A

    Journal of thrombosis and haemostasis : JTH

    2019  Volume 17, Issue 4, Page(s) 607–617

    Abstract: Essentials Loss of fibrinogen in zebrafish has been previously shown to result in adult onset hemorrhage Hemostatic defects were discovered in early ... ...

    Abstract Essentials Loss of fibrinogen in zebrafish has been previously shown to result in adult onset hemorrhage Hemostatic defects were discovered in early fga
    MeSH term(s) Afibrinogenemia/blood ; Afibrinogenemia/metabolism ; Animals ; Animals, Genetically Modified ; Fibrinogen/genetics ; Fibrinogen/metabolism ; Hemorrhage/blood ; Hemorrhage/genetics ; Hemostasis/genetics ; Humans ; NF-E2 Transcription Factor, p45 Subunit/genetics ; NF-E2 Transcription Factor, p45 Subunit/metabolism ; Synthetic Lethal Mutations ; Thrombocytopenia/blood ; Thrombocytopenia/genetics ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/deficiency ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
    Chemical Substances FGA protein, human ; NF-E2 Transcription Factor, p45 Subunit ; Zebrafish Proteins ; nfe2 protein, zebrafish ; Fibrinogen (9001-32-5)
    Language English
    Publishing date 2019-02-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1111/jth.14391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5805: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 295: Show issues

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  3. Article ; Online: Analysis of factor V in zebrafish demonstrates minimal levels needed for early hemostasis.

    Weyand, Angela C / Grzegorski, Steve J / Rost, Megan S / Lavik, Kari I / Ferguson, Allison C / Menegatti, Marzia / Richter, Catherine E / Asselta, Rosanna / Duga, Stefano / Peyvandi, Flora / Shavit, Jordan A

    Blood advances

    2019  Volume 3, Issue 11, Page(s) 1670–1680

    Abstract: In humans, coagulation factor V (FV) deficiency is a rare, clinically heterogeneous bleeding disorder, suggesting that genetic modifiers may contribute to disease expressivity. Zebrafish possess many distinct advantages including high fecundity, optical ... ...

    Abstract In humans, coagulation factor V (FV) deficiency is a rare, clinically heterogeneous bleeding disorder, suggesting that genetic modifiers may contribute to disease expressivity. Zebrafish possess many distinct advantages including high fecundity, optical clarity, external development, and homology with the mammalian hemostatic system, features that make it ideal for genetic studies. Our aim was to study the role of FV in zebrafish through targeted mutagenesis and apply the model to the study of human
    MeSH term(s) Animals ; Animals, Genetically Modified ; Disease Models, Animal ; Factor V/genetics ; Factor V/metabolism ; Hemorrhage/genetics ; Hemorrhage/metabolism ; Hemostasis ; Humans ; Thrombosis/genetics ; Thrombosis/metabolism ; Zebrafish/genetics ; Zebrafish/metabolism
    Chemical Substances Factor V (9001-24-5)
    Language English
    Publishing date 2019-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2018029066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7153: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy.

    Arden, Jessica D / Lavik, Kari I / Rubinic, Kaitlin A / Chiaia, Nicolas / Khuder, Sadik A / Howard, Marthe J / Nestor-Kalinoski, Andrea L / Alberts, Arthur S / Eisenmann, Kathryn M

    Molecular biology of the cell

    2015  Volume 26, Issue 21, Page(s) 3704–3718

    Abstract: The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous ...

    Abstract The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility. Historically, anti-invasion strategies focused upon mDia inhibition, whereas activation remained unexplored. The recent development of small molecules directly inhibiting or activating mDia-driven F-actin assembly that supports motility allows for exploration of their role in GBM. We used the formin inhibitor SMIFH2 and mDia agonists IMM-01/-02 and mDia2-DAD peptides, which disrupt autoinhibition, to examine the roles of mDia inactivation versus activation in GBM cell migration and invasion in vitro and in an ex vivo brain slice invasion model. Inhibiting mDia suppressed directional migration and spheroid invasion while preserving intrinsic random migration. mDia agonism abrogated both random intrinsic and directional migration and halted U87 spheroid invasion in ex vivo brain slices. Thus mDia agonism is a superior GBM anti-invasion strategy. We conclude that formin agonism impedes the most dangerous GBM component-tumor spread into surrounding healthy tissue. Formin activation impairs novel aspects of transformed cells and informs the development of anti-GBM invasion strategies.
    MeSH term(s) Adaptor Proteins, Signal Transducing/agonists ; Adaptor Proteins, Signal Transducing/biosynthesis ; Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Golgi Apparatus/drug effects ; Golgi Apparatus/metabolism ; Humans ; Neoplasm Invasiveness ; Rats ; Small Molecule Libraries/pharmacology ; Spheroids, Cellular
    Chemical Substances Adaptor Proteins, Signal Transducing ; DIAPH1 protein, human ; Small Molecule Libraries
    Language English
    Publishing date 2015-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E14-11-1502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2853: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 410: Show issues

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