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  1. Article ; Online: SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome.

    Zaffagni, Michela / Harris, Jenna M / Patop, Ines L / Pamudurti, Nagarjuna Reddy / Nguyen, Sinead / Kadener, Sebastian

    eLife

    2022  Volume 11

    Abstract: Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein ... ...

    Abstract Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of
    MeSH term(s) COVID-19/genetics ; Exoribonucleases/metabolism ; Humans ; RNA, Viral/metabolism ; SARS-CoV-2 ; Transcriptome ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism ; Virus Replication/genetics
    Chemical Substances RNA, Viral ; Viral Nonstructural Proteins ; Exoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2022-03-16
    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.71945
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome.

    Zaffagni, Michela / Harris, Jenna M / Patop, Ines L / Pamudurti, Nagarjuna Reddy / Nguyen, Sinead / Kadener, Sebastian

    bioRxiv : the preprint server for biology

    2022  

    Abstract: Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein ... ...

    Abstract Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1,000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.07.02.450964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Prospective isolation of NKX2-1-expressing human lung progenitors derived from pluripotent stem cells.

    Hawkins, Finn / Kramer, Philipp / Jacob, Anjali / Driver, Ian / Thomas, Dylan C / McCauley, Katherine B / Skvir, Nicholas / Crane, Ana M / Kurmann, Anita A / Hollenberg, Anthony N / Nguyen, Sinead / Wong, Brandon G / Khalil, Ahmad S / Huang, Sarah Xl / Guttentag, Susan / Rock, Jason R / Shannon, John M / Davis, Brian R / Kotton, Darrell N

    The Journal of clinical investigation

    2017  Volume 127, Issue 6, Page(s) 2277–2294

    Abstract: It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an ... ...

    Abstract It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered and developmentally differentiated NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers. After sorting to purity, these primordial lung progenitors exhibited lung epithelial maturation. In the absence of mesenchymal coculture support, this NKX2-1+ population was able to generate epithelial-only spheroids in defined 3D cultures. Alternatively, when recombined with fetal mouse lung mesenchyme, the cells recapitulated epithelial-mesenchymal developing lung interactions. We imaged these progenitors in real time and performed time-series global transcriptomic profiling and single-cell RNA sequencing as they moved through the earliest moments of lung lineage specification. The profiles indicated that evolutionarily conserved, stage-dependent gene signatures of early lung development are expressed in primordial human lung progenitors and revealed a CD47hiCD26lo cell surface phenotype that allows their prospective isolation from untargeted, patient-specific PSCs for further in vitro differentiation and future applications in regenerative medicine.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Separation ; Cells, Cultured ; Flow Cytometry ; Gene Expression Regulation, Enzymologic ; Humans ; Induced Pluripotent Stem Cells/physiology ; Mice ; Nuclear Proteins/metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors/metabolism ; Transcriptome
    Chemical Substances Nkx2-1 protein, mouse ; Nuclear Proteins ; Thyroid Nuclear Factor 1 ; Transcription Factors
    Language English
    Publishing date 2017-05-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI89950
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: A conserved Toll-like receptor-to-NF-κB signaling pathway in the endangered coral Orbicella faveolata.

    Williams, Leah M / Fuess, Lauren E / Brennan, Joseph J / Mansfield, Katelyn M / Salas-Rodriguez, Erick / Welsh, Julianne / Awtry, Jake / Banic, Sarah / Chacko, Cecilia / Chezian, Aarthia / Dowers, Donovan / Estrada, Felicia / Hsieh, Yu-Hsuan / Kang, Jiawen / Li, Wanwen / Malchiodi, Zoe / Malinowski, John / Matuszak, Sean / McTigue, Thomas /
    Mueller, David / Nguyen, Brian / Nguyen, Michelle / Nguyen, Phuong / Nguyen, Sinead / Njoku, Ndidi / Patel, Khusbu / Pellegrini, William / Pliakas, Tessa / Qadir, Deena / Ryan, Emma / Schiffer, Alex / Thiel, Amber / Yunes, Sarah A / Spilios, Kathryn E / Pinzón C, Jorge H / Mydlarz, Laura D / Gilmore, Thomas D

    Developmental and comparative immunology

    2018  Volume 79, Page(s) 128–136

    Abstract: Herein, we characterize the Toll-like receptor (TLR)-to-NF-κB innate immune pathway of Orbicella faveolata (Of), which is an ecologically important, disease-susceptible, reef-building coral. As compared to human TLRs, the intracellular TIR domain of Of- ... ...

    Abstract Herein, we characterize the Toll-like receptor (TLR)-to-NF-κB innate immune pathway of Orbicella faveolata (Of), which is an ecologically important, disease-susceptible, reef-building coral. As compared to human TLRs, the intracellular TIR domain of Of-TLR is most similar to TLR4, and it can interact in vitro with the human TLR4 adapter MYD88. Treatment of O. faveolata tissue with lipopolysaccharide, a ligand for mammalian TLR4, resulted in gene expression changes consistent with NF-κB pathway mobilization. Biochemical and cell-based assays revealed that Of-NF-κB resembles the mammalian non-canonical NF-κB protein p100 in that C-terminal truncation results in translocation of Of-NF-κB to the nucleus and increases its DNA-binding and transcriptional activation activities. Moreover, human IκB kinase (IKK) and Of-IKK can both phosphorylate conserved residues in Of-NF-κB in vitro and induce C-terminal processing of Of-NF-κB in vivo. These results are the first characterization of TLR-to-NF-κB signaling proteins in an endangered coral, and suggest that these corals have conserved innate immune pathways.
    MeSH term(s) Animals ; Anthozoa/immunology ; Biological Evolution ; Conserved Sequence/genetics ; Humans ; I-kappa B Kinase/metabolism ; Immunity, Innate ; Lipopolysaccharides/immunology ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Phosphorylation ; Protein Binding ; Signal Transduction ; Toll-Like Receptor 4/genetics ; Toll-Like Receptors/genetics ; Toll-Like Receptors/metabolism
    Chemical Substances Lipopolysaccharides ; MYD88 protein, human ; Myeloid Differentiation Factor 88 ; NF-kappa B ; TLR4 protein, human ; Toll-Like Receptor 4 ; Toll-Like Receptors ; I-kappa B Kinase (EC 2.7.11.10)
    Language English
    Publishing date 2018
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 752411-0
    ISSN 1879-0089 ; 0145-305X
    ISSN (online) 1879-0089
    ISSN 0145-305X
    DOI 10.1016/j.dci.2017.10.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1327: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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