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  1. Article: Sex differences in symptomatology and immune profiles of Long COVID.

    Silva, Julio / Takahashi, Takehiro / Wood, Jamie / Lu, Peiwen / Tabachnikova, Alexandra / Gehlhausen, Jeff R / Greene, Kerrie / Bhattacharjee, Bornali / Monteiro, Valter Silva / Lucas, Carolina / Dhodapkar, Rahul M / Tabacof, Laura / Peña-Hernandez, Mario / Kamath, Kathy / Mao, Tianyang / Mccarthy, Dayna / Medzhitov, Ruslan / van Dijk, David / Krumholz, Harlan M /
    Guan, Leying / Putrino, David / Iwasaki, Akiko

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 ... ...

    Abstract Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.29.24303568
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Directed evolution of the metalloproteinase inhibitor TIMP-1 reveals that its N- and C-terminal domains cooperate in matrix metalloproteinase recognition.

    Raeeszadeh-Sarmazdeh, Maryam / Greene, Kerrie A / Sankaran, Banumathi / Downey, Gregory P / Radisky, Derek C / Radisky, Evette S

    The Journal of biological chemistry

    2019  Volume 294, Issue 24, Page(s) 9476–9488

    Abstract: Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs), enzymes that contribute to cancer and many inflammatory and degenerative diseases. The TIMP N-terminal domain binds and inhibits an MMP catalytic ... ...

    Abstract Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs), enzymes that contribute to cancer and many inflammatory and degenerative diseases. The TIMP N-terminal domain binds and inhibits an MMP catalytic domain, but the role of the TIMP C-terminal domain in MMP inhibition is poorly understood. Here, we employed yeast surface display for directed evolution of full-length human TIMP-1 to develop MMP-3-targeting ultrabinders. By simultaneously incorporating diversity into both domains, we identified TIMP-1 variants that were up to 10-fold improved in binding MMP-3 compared with WT TIMP-1, with inhibition constants (
    MeSH term(s) Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Directed Molecular Evolution ; Humans ; Matrix Metalloproteinase 3/chemistry ; Matrix Metalloproteinase 3/genetics ; Matrix Metalloproteinase 3/metabolism ; Matrix Metalloproteinase Inhibitors/chemistry ; Matrix Metalloproteinase Inhibitors/metabolism ; Mutation ; Protein Binding ; Protein Conformation ; Protein Domains ; Tissue Inhibitor of Metalloproteinase-1/chemistry ; Tissue Inhibitor of Metalloproteinase-1/genetics ; Tissue Inhibitor of Metalloproteinase-1/metabolism ; Two-Hybrid System Techniques
    Chemical Substances Matrix Metalloproteinase Inhibitors ; TIMP1 protein, human ; Tissue Inhibitor of Metalloproteinase-1 ; MMP3 protein, human (EC 3.4.24.17) ; Matrix Metalloproteinase 3 (EC 3.4.24.17)
    Language English
    Publishing date 2019-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA119.008321
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Sex differences in symptomatology and immune profiles of Long COVID

    Silva, Julio / Takahashi, Takehiro / Wood, Jamie / Lu, Peiwen / Tabachnikova, Sasha / Gehlhausen, Jeffrey / Greene, Kerrie / Bhattacharjee, Bornali / Silva Monteiro, Valter / Lucas, Carolina / Dhodapkar, Rahul / Tabacof, Laura / Pena-Hernandez, Mario / Kamath, Kathy / Mao, Tianyang / Mccarthy, Dayna / Medzhitov, Ruslan / van Dijk, David / Krumholz, Harlan /
    Guan, Leying / Putrino, David / Iwasaki, Akiko

    medRxiv

    Abstract: Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection1-7. However, whether immunological traits underlying ... ...

    Abstract Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection1-7. However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals8 with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-β-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.
    Keywords covid19
    Language English
    Publishing date 2024-03-04
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2024.02.29.24303568
    Database COVID19

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  4. Article: Distinguishing features of Long COVID identified through immune profiling.

    Klein, Jon / Wood, Jamie / Jaycox, Jillian / Lu, Peiwen / Dhodapkar, Rahul M / Gehlhausen, Jeff R / Tabachnikova, Alexandra / Tabacof, Laura / Malik, Amyn A / Kamath, Kathy / Greene, Kerrie / Monteiro, Valter Silva / Peña-Hernandez, Mario / Mao, Tianyang / Bhattacharjee, Bornali / Takahashi, Takehiro / Lucas, Carolina / Silva, Julio / Mccarthy, Dayna /
    Breyman, Erica / Tosto-Mancuso, Jenna / Dai, Yile / Perotti, Emily / Akduman, Koray / Tzeng, Tiffany J / Xu, Lan / Yildirim, Inci / Krumholz, Harlan M / Shon, John / Medzhitov, Ruslan / Omer, Saad B / van Dijk, David / Ring, Aaron M / Putrino, David / Iwasaki, Akiko

    medRxiv : the preprint server for health sciences

    2022  

    Abstract: SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long ... ...

    Abstract SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.08.09.22278592
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Distinguishing features of long COVID identified through immune profiling.

    Klein, Jon / Wood, Jamie / Jaycox, Jillian R / Dhodapkar, Rahul M / Lu, Peiwen / Gehlhausen, Jeff R / Tabachnikova, Alexandra / Greene, Kerrie / Tabacof, Laura / Malik, Amyn A / Silva Monteiro, Valter / Silva, Julio / Kamath, Kathy / Zhang, Minlu / Dhal, Abhilash / Ott, Isabel M / Valle, Gabrielee / Peña-Hernández, Mario / Mao, Tianyang /
    Bhattacharjee, Bornali / Takahashi, Takehiro / Lucas, Carolina / Song, Eric / McCarthy, Dayna / Breyman, Erica / Tosto-Mancuso, Jenna / Dai, Yile / Perotti, Emily / Akduman, Koray / Tzeng, Tiffany J / Xu, Lan / Geraghty, Anna C / Monje, Michelle / Yildirim, Inci / Shon, John / Medzhitov, Ruslan / Lutchmansingh, Denyse / Possick, Jennifer D / Kaminski, Naftali / Omer, Saad B / Krumholz, Harlan M / Guan, Leying / Dela Cruz, Charles S / van Dijk, David / Ring, Aaron M / Putrino, David / Iwasaki, Akiko

    Nature

    2023  Volume 623, Issue 7985, Page(s) 139–148

    Abstract: Post-acute infection syndromes may develop after acute viral ... ...

    Abstract Post-acute infection syndromes may develop after acute viral disease
    MeSH term(s) Humans ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Biomarkers/blood ; Cross-Sectional Studies ; Herpesvirus 4, Human/immunology ; Hydrocortisone/blood ; Immunophenotyping ; Lymphocytes/immunology ; Machine Learning ; Myeloid Cells/immunology ; Post-Acute COVID-19 Syndrome/diagnosis ; Post-Acute COVID-19 Syndrome/immunology ; Post-Acute COVID-19 Syndrome/physiopathology ; Post-Acute COVID-19 Syndrome/virology ; SARS-CoV-2/immunology
    Chemical Substances Antibodies, Viral ; Biomarkers ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2023-09-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06651-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
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    Zs.MO 244: Show issues

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  6. Article ; Online: Distinguishing features of Long COVID identified through immune profiling

    Klein, Jon / Wood, Jamie / Jaycox, Jillian / Lu, Peiwen / Dhodapkar, Rahul M. / Gehlhausen, Jeffrey R. / Tabachnikova, Alexandra / Tabacof, Laura / Malik, Amyn A. / Kamath, Kathy / Greene, Kerrie / Silva Monteiro, Valter / Pena-Hernandez, Mario / Mao, Tianyang / Bhattacharjee, Bornali / Takahashi, Takehiro / Lucas, Carolina / Silva, Julio / Mccarthy, Dayna /
    Breyman, Erica / Tosto-Mancuso, Jenna / Dai, Yile / Perotti, Emily / Akduman, Koray / Tzeng, Tiffany / Xu, Lan / Yildirim, Inci / Krumholz, Harlan M. / Shon, John / Medzhitov, Ruslan / Omer, Saad B. / van Dijk, David / Ring, Aaron M. / Putrino, David / Iwasaki, Akiko

    medRxiv

    Abstract: SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, ...

    Abstract SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.
    Keywords covid19
    Language English
    Publishing date 2022-08-10
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.08.09.22278592
    Database COVID19

    Full text online

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