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  1. Article: Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

    Tung, Victoria Sook Keng / Mathews, Fasil / Boruk, Marina / Suppa, Gabrielle / Foronjy, Robert / Pato, Michele / Pato, Carlos / Knowles, James A / Evgrafov, Oleg V

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) ... ...

    Abstract Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) derived from superior or middle turbinates of patients with schizophrenia and control groups to study gene expression specific to schizophrenia. In this study, we compared single cell-RNA seq data from two CNON cell lines, one derived from an individual with schizophrenia (SCZ) and the other from a control group, with two biopsy samples from the middle turbinate (MT), also from an individual with SCZ and a control. In addition, we compared our data with previously published data from olfactory neuroepithelium (1). Our data demonstrated that CNON originated from a single cell type which is present both in middle turbinate and olfactory neuroepithelium. CNON express multiple markers of mesenchymal cells. In order to define relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data of embryonic brain (2) and found that the expression profile of CNON very closely matched one of the cell types in the embryonic brain. Finally, we evaluated differences between SCZ and control samples to assess usability and potential benefits of using single cell RNA-seq of CNON to study etiology of schizophrenia.
    Language English
    Publishing date 2023-03-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.28.534295
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

    Tung, Victoria Sook Keng / Mathews, Fasil / Boruk, Marina / Suppa, Gabrielle / Foronjy, Robert / Pato, Michele T / Pato, Carlos N / Knowles, James A / Evgrafov, Oleg V

    International journal of molecular sciences

    2023  Volume 24, Issue 20

    Abstract: The study of neurodevelopmental molecular mechanisms in schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously utilized cell lines with neural progenitor properties (CNON) ... ...

    Abstract The study of neurodevelopmental molecular mechanisms in schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously utilized cell lines with neural progenitor properties (CNON) derived from the superior or middle turbinates of patients with schizophrenia and control groups to study schizophrenia-specific gene expression. In this study, we analyzed single-cell RNA seq data from two CNON cell lines (one derived from an individual with schizophrenia (SCZ) and the other from a control group) and two biopsy samples from the middle turbinate (MT) (also from an individual with SCZ and a control). We compared our data with previously published data regarding the olfactory neuroepithelium and demonstrated that CNON originated from a single cell type present both in middle turbinate and the olfactory neuroepithelium and expressed in multiple markers of mesenchymal cells. To define the relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data derived from an embryonic brain and found that the expression profile of the CNON closely matched the expression profile one of the cell types in the embryonic brain. Finally, we evaluated the differences between SCZ and control samples to assess the utility and potential benefits of using CNON single-cell RNA seq to study the etiology of schizophrenia.
    MeSH term(s) Humans ; Turbinates/pathology ; Schizophrenia/genetics ; Schizophrenia/metabolism ; Cells, Cultured ; Neurons/metabolism ; Neural Stem Cells/metabolism
    Language English
    Publishing date 2023-10-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms242015339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Inactivation influences the extent of inhibition of voltage-gated Ca

    Allam, Salma / Levenson-Palmer, Rose / Chia Chang, Zuleen / Kaur, Sukhjinder / Cernuda, Bryan / Raman, Ananya / Booth, Audrey / Dobbins, Scott / Suppa, Gabrielle / Yang, Jian / Buraei, Zafir

    Frontiers in physiology

    2023  Volume 14, Page(s) 1155976

    Abstract: Voltage-gated ... ...

    Abstract Voltage-gated Ca
    Language English
    Publishing date 2023-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2023.1155976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The molecular determinants of R-roscovitine block of hERG channels.

    Cernuda, Bryan / Fernandes, Christopher Thomas / Allam, Salma Mohamed / Orzillo, Matthew / Suppa, Gabrielle / Chia Chang, Zuleen / Athanasopoulos, Demosthenes / Buraei, Zafir

    PloS one

    2019  Volume 14, Issue 9, Page(s) e0217733

    Abstract: Human ether-à-go-go-related gene (Kv11.1, or hERG) is a potassium channel that conducts the delayed rectifier potassium current (IKr) during the repolarization phase of cardiac action potentials. hERG channels have a larger pore than other K+channels and ...

    Abstract Human ether-à-go-go-related gene (Kv11.1, or hERG) is a potassium channel that conducts the delayed rectifier potassium current (IKr) during the repolarization phase of cardiac action potentials. hERG channels have a larger pore than other K+channels and can trap many unintended drugs, often resulting in acquired LQTS (aLQTS). R-roscovitine is a cyclin-dependent kinase (CDK) inhibitor that induces apoptosis in colorectal, breast, prostate, multiple myeloma, other cancer cell lines, and tumor xenografts, in micromolar concentrations. It is well tolerated in phase II clinical trials. R-roscovitine inhibits open hERG channels but does not become trapped in the pore. Two-electrode voltage clamp recordings from Xenopus oocytes expressing wild-type (WT) or hERG pore mutant channels (T623A, S624A, Y652A, F656A) demonstrated that compared to WT hERG, T623A, Y652A, and F656A inhibition by 200 μM R-roscovitine was ~ 48%, 29%, and 73% weaker, respectively. In contrast, S624A hERG was inhibited more potently than WT hERG, with a ~ 34% stronger inhibition. These findings were further supported by the IC50 values, which were increased for T623A, Y652A and F656A (by ~5.5, 2.75, and 42 fold respectively) and reduced 1.3 fold for the S624A mutant. Our data suggest that while T623, Y652, and F656 are critical for R-roscovitine-mediated inhibition, S624 may not be. Docking studies further support our findings. Thus, R-roscovitine's relatively unique features, coupled with its tolerance in clinical trials, could guide future drug screens.
    MeSH term(s) Animals ; Dose-Response Relationship, Drug ; Drug Discovery ; Ether-A-Go-Go Potassium Channels/antagonists & inhibitors ; Ether-A-Go-Go Potassium Channels/chemistry ; Ether-A-Go-Go Potassium Channels/genetics ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Molecular Structure ; Mutation ; Oocytes/drug effects ; Oocytes/metabolism ; Potassium Channel Blockers/chemistry ; Potassium Channel Blockers/pharmacology ; Protein Conformation ; Structure-Activity Relationship
    Chemical Substances Ether-A-Go-Go Potassium Channels ; Potassium Channel Blockers
    Language English
    Publishing date 2019-09-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0217733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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