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  1. AU="Zhu, Daniel Y"
  2. AU="Kovatich, Albert J."
  3. AU="Judith Romero-Gallo"
  4. AU="Krishnaraj Rajaram"
  5. AU=McKay Andrew
  6. AU="Price, Leigh"
  7. AU="Banur Boynukara"
  8. AU="Olsson, Marita"
  9. AU="Gevorkyan, Gevork"
  10. AU="Francis, Jill"
  11. AU="Katori, Chiaki"
  12. AU="Anderson, Karly N"
  13. AU=Sheikh Fatima
  14. AU="Machado, Clarissa Maria Goncalves" AU="Machado, Clarissa Maria Goncalves"
  15. AU="Goldfaden, Rebecca F"
  16. AU="Jacques, Simon"
  17. AU="Calatayud, David G"
  18. AU="Yan, Dingfei"
  19. AU="Rippin, Ido"
  20. AU="Krista M. Pullen"
  21. AU="Higo, Tomoya"
  22. AU="Bremadesam Raman, Lakshmi"
  23. AU="Duffner, P K"
  24. AU="Walsh, Jacinta"

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  1. Artikel ; Online: AutoTransOP: translating omics signatures without orthologue requirements using deep learning.

    Meimetis, Nikolaos / Pullen, Krista M / Zhu, Daniel Y / Nilsson, Avlant / Hoang, Trong Nghia / Magliacane, Sara / Lauffenburger, Douglas A

    NPJ systems biology and applications

    2024  Band 10, Heft 1, Seite(n) 13

    Abstract: The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human ... ...

    Abstract The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human biology as evidenced by the predominant likelihood of clinical trial failure. To address this problem, we developed AutoTransOP, a neural network autoencoder framework, to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information for different contexts can be identified without the typically imposed requirement of matched orthologues. This approach was found in general to perform at least as well as current alternative methods in identifying animal/culture-specific molecular features predictive of other contexts-most importantly without requiring homology matching. For an especially challenging test case, we successfully applied our framework to a set of inter-species vaccine serology studies, where 1-to-1 mapping between human and non-human primate features does not exist.
    Mesh-Begriff(e) Animals ; Deep Learning ; Neural Networks, Computer
    Sprache Englisch
    Erscheinungsdatum 2024-01-29
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2056-7189
    ISSN (online) 2056-7189
    DOI 10.1038/s41540-024-00341-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Microtubule Growth Rates Are Sensitive to Global and Local Changes in Microtubule Plus-End Density.

    Geisterfer, Zachary M / Zhu, Daniel Y / Mitchison, Timothy J / Oakey, John / Gatlin, Jesse C

    Current biology : CB

    2020  Band 30, Heft 15, Seite(n) 3016–3023.e3

    Abstract: The microtubule cytoskeleton plays critically important roles in numerous cellular functions in eukaryotes, and it does so across a functionally diverse and morphologically disparate range of cell types [1]. In these roles, microtubule assemblies must ... ...

    Abstract The microtubule cytoskeleton plays critically important roles in numerous cellular functions in eukaryotes, and it does so across a functionally diverse and morphologically disparate range of cell types [1]. In these roles, microtubule assemblies must adopt distinct morphologies and physical dimensions to perform specific functions [2-5]. As such, these macromolecular assemblies-as well as the dynamics of the individual microtubule polymers from which they are made-must scale and change in accordance with cell size, geometry, and function. Microtubules in cells typically assemble to a steady state in mass, leaving enough of their tubulin subunits soluble to allow rapid growth and turnover. This suggests some negative feedback that limits the extent of assembly, for example, decrease in growth rate, or increase in catastrophe rate, as the soluble subunit pool decreases. Although these ideas have informed the field for decades, they have not been observed experimentally. Here, we describe the application of an experimental approach that combines cell-free extracts with photo-patterned hydrogel micro-enclosures as a means to investigate microtubule dynamics in cytoplasmic volumes of defined size and shape. Our measurements reveal a negative correlation between microtubule plus-end density and microtubule growth rates and suggest that these rates are sensitive to the presence of nearby growing ends.
    Mesh-Begriff(e) Animals ; Cell Size ; Cell-Free System ; Cytoplasm/metabolism ; Hydrogels ; Microtubules/chemistry ; Microtubules/metabolism ; Microtubules/physiology ; Solubility ; Tubulin/metabolism ; Xenopus
    Chemische Substanzen Hydrogels ; Tubulin
    Sprache Englisch
    Erscheinungsdatum 2020-06-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2020.05.056
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3208: Hefte anzeigen Standort:
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  3. Artikel ; Online: Defining the determinants of protection against SARS-CoV-2 infection and viral control in a dose-down Ad26.CoV2.S vaccine study in nonhuman primates.

    Zhu, Daniel Y / Gorman, Matthew J / Yuan, Dansu / Yu, Jingyou / Mercado, Noe B / McMahan, Katherine / Borducchi, Erica N / Lifton, Michelle / Liu, Jinyan / Nampanya, Felix / Patel, Shivani / Peter, Lauren / Tostanoski, Lisa H / Pessaint, Laurent / Van Ry, Alex / Finneyfrock, Brad / Velasco, Jason / Teow, Elyse / Brown, Renita /
    Cook, Anthony / Andersen, Hanne / Lewis, Mark G / Lauffenburger, Douglas A / Barouch, Dan H / Alter, Galit

    PLoS biology

    2022  Band 20, Heft 5, Seite(n) e3001609

    Abstract: Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust ... ...

    Abstract Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.
    Mesh-Begriff(e) Ad26COVS1 ; Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Primates ; Receptors, Fc ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
    Chemische Substanzen Ad26COVS1 (JT2NS6183B) ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Receptors, Fc ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2022-05-05
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3001609
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6193: Hefte anzeigen Standort:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Artikel ; Online: Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors.

    Chen, Rita E / Gorman, Matthew J / Zhu, Daniel Y / Carreño, Juan Manuel / Yuan, Dansu / VanBlargan, Laura A / Burdess, Samantha / Lauffenburger, Douglas A / Kim, Wooseob / Turner, Jackson S / Droit, Lindsay / Handley, Scott A / Chahin, Salim / Deepak, Parakkal / O'Halloran, Jane A / Paley, Michael A / Presti, Rachel M / Wu, Gregory F / Krammer, Florian /
    Alter, Galit / Ellebedy, Ali H / Kim, Alfred H J / Diamond, Michael S

    Med (New York, N.Y.)

    2021  Band 2, Heft 12, Seite(n) 1327–1341.e4

    Abstract: Background: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy.: ... ...

    Abstract Background: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy.
    Methods: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine.
    Findings: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFi-treated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold.
    Conclusions: Vaccine boosting or administration of long-acting prophylaxis (
    Funding: This study was supported by grants and contracts from the NIH (R01 AI157155, R01AI151178, and HHSN75N93019C00074; NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014; and Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051).
    Mesh-Begriff(e) Antibodies, Viral ; BNT162 Vaccine ; COVID-19 Vaccines/therapeutic use ; Hepatitis Delta Virus ; Humans ; RNA, Messenger/genetics ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Tumor Necrosis Factor-alpha ; Vaccines, Synthetic ; mRNA Vaccines ; COVID-19 Drug Treatment
    Chemische Substanzen Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Spike Glycoprotein, Coronavirus ; Tumor Necrosis Factor-alpha ; Vaccines, Synthetic ; mRNA Vaccines ; spike protein, SARS-CoV-2 ; BNT162 Vaccine (N38TVC63NU)
    Sprache Englisch
    Erscheinungsdatum 2021-11-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2021.11.004
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Reduced antibody activity against SARS-CoV-2 B.1.617.2 Delta virus in serum of mRNA-vaccinated patients receiving TNF-alpha inhibitors

    Chen, Rita E / Gorman, Matthew J / Zhu, Daniel Y / Carreno, Juan Manuel / Yuan, Dansu / VanBlargan, Laura A / Burdess, Samantha / Lauffenburger, Douglas A / Kim, Wooseob / Turner, Jackson S / Droit, Lindsay / Handley, Scott A / Chahin, Salim / Deepak, Parakkal / O'Halloran, Jane / Paley, Michael / Presti, Rachel / Wu, Gregory F / Krammer, Florian /
    Alter, Galit / Ellebedy, Ali / Kim, Alfred Hyoungju / Diamond, Michael S

    medRxiv

    Abstract: Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against ... ...

    Abstract Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against emerging variants of concern in this population. Here, we assessed a cohort of 74 CID patients treated as monotherapy with chronic immunosuppressive drugs for functional antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with Pfizer mRNA BNT162b2 vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with TNF-alpha inhibitors, and this pattern appeared worse against the B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of the majority of CID patients fell below the presumed threshold correlate for antibody-mediated protection. Thus, further vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-09-29
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.09.28.21264250
    Datenquelle COVID19

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