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  1. Article ; Online: Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients

    Gomes, Claudia / Zuniga, Marisol / Crotty, Kelly A. / Qian, Kun / Hsu Lin, Lawrence / Argyropoulos, Kimon / Li, Huilin / Cotzia, Paolo / Rodriguez, Ana

    medRxiv

    Abstract: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease and death, however the mechanisms of pathogenesis in these patients remain poorly understood. High levels of autoimmune antibodies have been observed ... ...

    Abstract Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease and death, however the mechanisms of pathogenesis in these patients remain poorly understood. High levels of autoimmune antibodies have been observed frequently in coronavirus disease (COVID-19) patients but their specific contribution to disease severity and clinical manifestations remain unknown. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. The statistical relation of autoantibody levels to death, disease severity and specific pathologies was determined using high-throughput data analysis of 118 clinical parameters for all patients. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 41%) of patients with COVID-19 compared to uninfected controls. Anti-DNA antibodies determined upon hospital admission were high in 16% of patients and correlated strongly with later development of severe disease, showing a positive predictive value of 89.5% and accounting for 22% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as a predictive biomarker for disease severity and specific clinical manifestations.
    Keywords covid19
    Language English
    Publishing date 2021-01-04
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.01.04.20249054
    Database COVID19

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  2. Article ; Online: Structurally Conserved Domains between Flavivirus and Alphavirus Fusion Glycoproteins Contribute to Replication and Infectious-Virion Production.

    Rangel, Margarita V / Catanzaro, Nicholas / Thannickal, Sara A / Crotty, Kelly A / Noval, Maria G / Johnson, Katherine E E / Ghedin, Elodie / Lazear, Helen M / Stapleford, Kenneth A

    Journal of virology

    2021  Volume 96, Issue 2, Page(s) e0177421

    Abstract: Alphaviruses and flaviviruses have class II fusion glycoproteins that are essential for virion assembly and infectivity. Importantly, the tip of domain II is structurally conserved between the alphavirus and flavivirus fusion proteins, yet whether these ... ...

    Abstract Alphaviruses and flaviviruses have class II fusion glycoproteins that are essential for virion assembly and infectivity. Importantly, the tip of domain II is structurally conserved between the alphavirus and flavivirus fusion proteins, yet whether these structural similarities between virus families translate to functional similarities is unclear. Using
    MeSH term(s) A549 Cells ; Alphavirus/drug effects ; Alphavirus/physiology ; Ammonium Chloride/pharmacology ; Animals ; Culicidae/virology ; Flavivirus/drug effects ; Flavivirus/physiology ; Humans ; Interferon Type I/deficiency ; Mice ; Mice, Mutant Strains ; Mutation ; Protein Domains ; Viral Fusion Proteins/chemistry ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/metabolism ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism ; Virion/genetics ; Virion/metabolism ; Virus Assembly/genetics ; Virus Internalization/drug effects ; Virus Replication/genetics ; Zika Virus/drug effects ; Zika Virus/physiology ; Zika Virus Infection/virology
    Chemical Substances Interferon Type I ; Viral Fusion Proteins ; Viral Nonstructural Proteins ; Ammonium Chloride (01Q9PC255D)
    Language English
    Publishing date 2021-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01774-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 609: Show issues Location:
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  3. Article ; Online: Design of a Multiuse Photoreactor To Enable Visible-Light Photocatalytic Chemical Transformations and Labeling in Live Cells.

    Bissonnette, Noah B / Ryu, Keun Ah / Reyes-Robles, Tamara / Wilhelm, Sharon / Tomlinson, Jake H / Crotty, Kelly A / Hett, Erik C / Roberts, Lee R / Hazuda, Daria J / Jared Willis, M / Oslund, Rob C / Fadeyi, Olugbeminiyi O

    Chembiochem : a European journal of chemical biology

    2020  Volume 21, Issue 24, Page(s) 3555–3562

    Abstract: Despite the growing use of visible-light photochemistry in both chemistry and biology, no general low-heat photoreactor for use across these different disciplines exists. Herein, we describe the design and use of a standardized photoreactor for visible- ... ...

    Abstract Despite the growing use of visible-light photochemistry in both chemistry and biology, no general low-heat photoreactor for use across these different disciplines exists. Herein, we describe the design and use of a standardized photoreactor for visible-light-driven activation and photocatalytic chemical transformations. Using this single benchtop photoreactor, we performed photoredox reactions across multiple visible light wavelengths, a high-throughput photocatalytic cross-coupling reaction, and in vitro labeling of proteins and live cells. Given the success of this reactor in all tested applications, we envision that this multi-use photoreactor will be widely used in biology, chemical biology, and medicinal chemistry settings.
    MeSH term(s) Biotin/analysis ; Catalysis ; Cell Line, Tumor ; Equipment Design ; Humans ; Light ; Molecular Structure ; Photobioreactors ; Photochemical Processes ; Tyramine/analogs & derivatives ; Tyramine/chemical synthesis ; Tyramine/chemistry
    Chemical Substances Biotin (6SO6U10H04) ; Tyramine (X8ZC7V0OX3)
    Language English
    Publishing date 2020-09-16
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202000392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19.

    Gomes, Claudia / Zuniga, Marisol / Crotty, Kelly A / Qian, Kun / Tovar, Nubia Catalina / Lin, Lawrence Hsu / Argyropoulos, Kimon V / Clancy, Robert / Izmirly, Peter / Buyon, Jill / Lee, David C / Yasnot-Acosta, Maria Fernanda / Li, Huilin / Cotzia, Paolo / Rodriguez, Ana

    Life science alliance

    2021  Volume 4, Issue 11

    Abstract: High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients ... ...

    Abstract High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibodies, Antinuclear/blood ; Antibodies, Antinuclear/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; Biomarkers ; COVID-19/immunology ; COVID-19/metabolism ; DNA/chemistry ; DNA/immunology ; Erythrocytes/immunology ; Female ; Humans ; Male ; Middle Aged ; Phosphatidylserines/immunology ; Prognosis ; Retrospective Studies ; SARS-CoV-2/isolation & purification ; Severity of Illness Index
    Chemical Substances Antibodies, Antinuclear ; Autoantibodies ; Biomarkers ; Phosphatidylserines ; DNA (9007-49-2)
    Language English
    Publishing date 2021-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202101180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Detection of cell-cell interactions via photocatalytic cell tagging.

    Oslund, Rob C / Reyes-Robles, Tamara / White, Cory H / Tomlinson, Jake H / Crotty, Kelly A / Bowman, Edward P / Chang, Dan / Peterson, Vanessa M / Li, Lixia / Frutos, Silvia / Vila-Perelló, Miquel / Vlerick, David / Cromie, Karen / Perlman, David H / Ingale, Sampat / Hara, Samantha D O' / Roberts, Lee R / Piizzi, Grazia / Hett, Erik C /
    Hazuda, Daria J / Fadeyi, Olugbeminiyi O

    Nature chemical biology

    2022  Volume 18, Issue 8, Page(s) 850–858

    Abstract: The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies ...

    Abstract The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies leveraging therapeutic-based modalities to profile intercellular environments offer opportunities to study cell-cell interactions with molecular-level insight. We introduce photocatalytic cell tagging (PhoTag) for interrogating cell-cell interactions using single-domain antibodies (VHHs) conjugated to photoactivatable flavin-based cofactors. Following irradiation with visible light, the flavin photocatalyst generates phenoxy radical tags for targeted labeling. Using this technology, we demonstrate selective synaptic labeling across the PD-1/PD-L1 axis in antigen-presenting cell-T cell systems. In combination with multiomics single-cell sequencing, we monitored interactions between peripheral blood mononuclear cells and Raji PD-L1 B cells, revealing differences in transient interactions with specific T cell subtypes. The utility of PhoTag in capturing cell-cell interactions will enable detailed profiling of intercellular communication across different biological systems.
    MeSH term(s) B7-H1 Antigen ; Cell Communication ; Flavins ; Immunotherapy ; Leukocytes, Mononuclear
    Chemical Substances B7-H1 Antigen ; Flavins
    Language English
    Publishing date 2022-06-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/s41589-022-01044-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 90: Show issues

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