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Article ; Online: Serological Markers of SARS-CoV-2 Reinfection.

Siddiqui, Sameed M / Bowman, Kathryn A / Zhu, Alex L / Fischinger, Stephanie / Beger, Samuel / Maron, Jenny S / Bartsch, Yannic C / Atyeo, Caroline / Gorman, Matthew J / Yanis, Ahmad / Hultquist, Judd F / Lorenzo-Redondo, Ramon / Ozer, Egon A / Simons, Lacy M / Talj, Rana / Rankin, Danielle A / Chapman, Lindsay / Meade, Kyle / Steinhart, Jordan /

Mullane, Sean / Siebert, Suzanne / Streeck, Hendrik / Sabeti, Pardis / Halasa, Natasha / Musk, Elon R / Barouch, Dan H / Menon, Anil S / Nilles, Eric J / Lauffenburger, Douglas A / Alter, Galit

mBio

2022 Volume 13, Issue 1, Page(s) e0214121

Abstract: As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting ... ...

Abstract	As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks.
MeSH term(s)	Animals ; Humans ; Reinfection ; Macaca mulatta ; SARS-CoV-2 ; COVID-19 ; Immunoglobulin G ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Immunoglobulin G ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02141-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination.

Gorman, Matthew J / Patel, Nita / Guebre-Xabier, Mimi / Zhu, Alex L / Atyeo, Caroline / Pullen, Krista M / Loos, Carolin / Goez-Gazi, Yenny / Carrion, Ricardo / Tian, Jing-Hui / Yuan, Dansu / Bowman, Kathryn A / Zhou, Bin / Maciejewski, Sonia / McGrath, Marisa E / Logue, James / Frieman, Matthew B / Montefiori, David / Mann, Colin /

Schendel, Sharon / Amanat, Fatima / Krammer, Florian / Saphire, Erica Ollmann / Lauffenburger, Douglas A / Greene, Ann M / Portnoff, Alyse D / Massare, Michael J / Ellingsworth, Larry / Glenn, Gregory / Smith, Gale / Alter, Galit

Cell reports. Medicine

2021 Volume 2, Issue 9, Page(s) 100405

Abstract: Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of ... ...

Abstract	Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single- or two-dose regimen. Both antigen dose and boosting significantly altered neutralization titers and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were associated with distinct levels of protection in the upper and lower respiratory tract. Moreover, NVX-CoV2373 elicited antibodies that functionally targeted emerging SARS-CoV-2 variants. Collectively, the data presented here suggest that a single dose may prevent disease via combined Fc/Fab functions but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.
MeSH term(s)	Animals ; Antibodies, Neutralizing/drug effects ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/virology ; COVID-19 Vaccines/immunology ; Dose-Response Relationship, Immunologic ; Female ; Immunity, Humoral/immunology ; Immunogenicity, Vaccine ; Immunoglobulin Fab Fragments/immunology ; Immunoglobulin Fc Fragments/immunology ; Macaca mulatta ; Male ; Nanoparticles ; Primates/immunology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Saponins/immunology ; Spike Glycoprotein, Coronavirus ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin Fab Fragments ; Immunoglobulin Fc Fragments ; Matrix-M ; Saponins ; Spike Glycoprotein, Coronavirus ; spike glycoprotein, SARS-CoV ; NVX-CoV2373 adjuvated lipid nanoparticle (2SCD8Q63PF)
Language	English
Publishing date	2021-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2021.100405
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.

Kaneko, Naoki / Kuo, Hsiao-Hsuan / Boucau, Julie / Farmer, Jocelyn R / Allard-Chamard, Hugues / Mahajan, Vinay S / Piechocka-Trocha, Alicja / Lefteri, Kristina / Osborn, Matthew / Bals, Julia / Bartsch, Yannic C / Bonheur, Nathalie / Caradonna, Timothy M / Chevalier, Josh / Chowdhury, Fatema / Diefenbach, Thomas J / Einkauf, Kevin / Fallon, Jon / Feldman, Jared /

Finn, Kelsey K / Garcia-Broncano, Pilar / Hartana, Ciputra Adijaya / Hauser, Blake M / Jiang, Chenyang / Kaplonek, Paulina / Karpell, Marshall / Koscher, Eric C / Lian, Xiaodong / Liu, Hang / Liu, Jinqing / Ly, Ngoc L / Michell, Ashlin R / Rassadkina, Yelizaveta / Seiger, Kyra / Sessa, Libera / Shin, Sally / Singh, Nishant / Sun, Weiwei / Sun, Xiaoming / Ticheli, Hannah J / Waring, Michael T / Zhu, Alex L / Alter, Galit / Li, Jonathan Z / Lingwood, Daniel / Schmidt, Aaron G / Lichterfeld, Mathias / Walker, Bruce D / Yu, Xu G / Padera, Robert F / Pillai, Shiv

Cell

2020 Volume 183, Issue 1, Page(s) 143–157.e13

Abstract: Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 ... ...

Abstract	Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6
MeSH term(s)	Aged ; Aged, 80 and over ; B-Lymphocytes/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Female ; Germinal Center/immunology ; Germinal Center/pathology ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/immunology ; Proto-Oncogene Proteins c-bcl-6/genetics ; Proto-Oncogene Proteins c-bcl-6/metabolism ; Spleen/immunology ; Spleen/pathology ; T-Lymphocytes, Helper-Inducer/immunology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	BCL6 protein, human ; Proto-Oncogene Proteins c-bcl-6 ; Tumor Necrosis Factor-alpha
Keywords	covid19
Language	English
Publishing date	2020-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2020.08.025
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Article ; Online: The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19.

Kaneko, Naoki / Kuo, Hsiao-Hsuan / Boucau, Julie / Farmer, Jocelyn R / Allard-Chamard, Hugues / Mahajan, Vinay S / Piechocka-Trocha, Alicja / Lefteri, Kristina / Osborn, Matt / Bals, Julia / Bartsch, Yannic C / Bonheur, Nathalie / Caradonna, Timothy M / Chevalier, Josh / Chowdhury, Fatema / Diefenbach, Thomas J / Einkauf, Kevin / Fallon, Jon / Feldman, Jared /

Finn, Kelsey K / Garcia-Broncano, Pilar / Hartana, Ciputra Adijaya / Hauser, Blake M / Jiang, Chenyang / Kaplonek, Paulina / Karpell, Marshall / Koscher, Eric C / Lian, Xiaodong / Liu, Hang / Liu, Jinqing / Ly, Ngoc L / Michell, Ashlin R / Rassadkina, Yelizaveta / Seiger, Kyra / Sessa, Libera / Shin, Sally / Singh, Nishant / Sun, Weiwei / Sun, Xiaoming / Ticheli, Hannah J / Waring, Michael T / Zhu, Alex L / Li, Jonathan / Lingwood, Daniel / Schmidt, Aaron G / Lichterfeld, Matthias / Walker, Bruce D / Yu, Xu / Padera, Robert F / Pillai, Shiv

SSRN

2020 , Page(s) 3652322

Abstract: Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed ... ...

Abstract	Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+TFH cell differentiation together with an increase in T-bet+TH1 cells and aberrant extra-follicular TNF-a accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections and suggest that achieving herd immunity through natural infection may be difficult. Funding: This work was supported by NIH U19 AI110495 to SP, NIH R01 AI146779 to AGS, NIH R01AI137057 and DP2DA042422 to DL, BMH was supported by NIGMS T32 GM007753, TMC was supported by T32 AI007245. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged. Conflict of Interest: None. Ethical Approval: This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women's Hospital.
Keywords	covid19
Language	English
Publishing date	2020-07-16
Publishing country	United States
Document type	Preprint
ISSN	1556-5068
ISSN (online)	1556-5068
DOI	10.2139/ssrn.3652322
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Article: Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19

Cell. 2020 Oct. 01, v. 183, no. 1

2020

Institution	the Massachusetts Consortium on Pathogen Readiness Specimen Working Group
Abstract	Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6⁺ germinal center B cells but preservation of AID⁺ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6⁺ TFH cell differentiation together with an increase in T-bet⁺ TH₁ cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific “disease-related” B cell populations. These data identify defective Bcl-6⁺ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.
Keywords	B-lymphocytes ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antibodies ; cell differentiation ; disease severity ; durability ; etiology ; herd immunity ; humans ; lymph ; lymph nodes
Language	English
Dates of publication	2020-1001
Size	p. 143-157.e13.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2020.08.025
Database	NAL-Catalogue (AGRICOLA)

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Article: The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19

Kaneko, Naoki Kuo Hsiao-Hsuan Boucau Julie Farmer Jocelyn R. / Allard-Chamard, Hugues Mahajan Vinay S. / Piechocka-Trocha, Alicja Lefteri Kristina Osborn Matt Bals Julia Bartsch Yannic C. / Bonheur, Nathalie Caradonna Timothy M. / Chevalier, Josh Chowdhury Fatema Diefenbach Thomas J. / Einkauf, Kevin Fallon Jon Feldman Jared Finn Kelsey K. / Garcia-Broncano, Pilar Hartana Ciputra Adijaya Hauser Blake M. / Jiang, Chenyang Kaplonek Paulina Karpell Marshall Koscher Eric C. / Lian, Xiaodong Liu Hang Liu Jinqing Ly Ngoc L. / Michell, Ashlin R. / Rassadkina, Yelizaveta Seiger Kyra Sessa Libera Shin Sally Singh Nishant Sun Weiwei Sun Xiaoming Ticheli Hannah J. / Waring, Michael T. / Zhu, Alex L. / Li, Jonathan Lingwood Daniel Schmidt Aaron G. / Lichterfeld, Matthias Walker Bruce D. / Yu, Xu Padera Robert F. / Pillai, Shiv Group Massachusetts Consortium on Pathogen Readiness Specimen Working

Abstract: Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics To address the underlying etiology, we ... ...

Abstract	Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics To address the underlying etiology, we ex
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #1683
Database	COVID19

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Article: The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19

Kaneko, Naoki / Kuo, Hsiao-Hsuan / Boucau, Julie / Farmer, Jocelyn R. / Allard-Chamard, Hugues / Mahajan, Vinay S. / Piechocka-Trocha, Alicja / Lefteri, Kristina / Osborn, Matt / Bals, Julia / Bartsch, Yannic C. / Bonheur, Nathalie / Caradonna, Timothy M. / Chevalier, Josh / Chowdhury, Fatema / Diefenbach, Thomas J. / Einkauf, Kevin / Fallon, Jon / Feldman, Jared /

Finn, Kelsey K. / Garcia-Broncano, Pilar / Hartana, Ciputra Adijaya / Hauser, Blake M. / Jiang, Chenyang / Kaplonek, Paulina / Karpell, Marshall / Koscher, Eric C. / Lian, Xiaodong / Liu, Hang / Liu, Jinqing / Ly, Ngoc L. / Michell, Ashlin R. / Rassadkina, Yelizaveta / Seiger, Kyra / Sessa, Libera / Shin, Sally / Singh, Nishant / Sun, Weiwei / Sun, Xiaoming / Ticheli, Hannah J. / Waring, Michael T. / Zhu, Alex L. / Li, Jonathan / Lingwood, Daniel / Schmidt, Aaron G. / Lichterfeld, Matthias / Walker, Bruce D. / Yu, Xu / Padera, Robert F. / Pillai, Shiv / Group, Massachusetts Consortium On Pathogen Readiness Specimen Working

SSRN

Abstract: Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed ... ...

Abstract	Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells Absence of germinal centers correlated with an early specific block in Bcl-6+TFH cell differentiation together with an increase in T-bet+TH1 cells and aberrant extra-follicular TNF-a accumulation Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations These data identify defective Bcl-6+TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections and suggest that achieving herd immunity through natural infection may be difficult Funding: This work was supported by NIH U19 AI110495 to SP, NIH R01 AI146779 to AGS, NIH R01AI137057 and DP2DA042422 to DL, BMH was supported by NIGMS T32 GM007753, TMC was supported by T32 AI007245 Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged Conflict of Interest: None Ethical Approval: This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women's Hospital
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #693389
Database	COVID19

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Article: Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19

Cell

Abstract	Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #720447
Database	COVID19

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Article ; Online: The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19

SSRN Electronic Journal ; ISSN 1556-5068

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.2139/ssrn.3652322
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19

Kaneko, Naoki / Kuo, Hsiao-Hsuan / Boucau, Julie / Farmer, Jocelyn R. / Allard-Chamard, Hugues / Mahajan, Vinay S. / Piechocka-Trocha, Alicja / Lefteri, Kristina / Osborn, Matthew / Bals, Julia / Bartsch, Yannic C. / Bonheur, Nathalie / Caradonna, Timothy M. / Chevalier, Josh / Chowdhury, Fatema / Diefenbach, Thomas J. / Einkauf, Kevin / Fallon, Jon / Feldman, Jared /

Finn, Kelsey K. / Garcia-Broncano, Pilar / Hartana, Ciputra Adijaya / Hauser, Blake M. / Jiang, Chenyang / Kaplonek, Paulina / Karpell, Marshall / Koscher, Eric C. / Lian, Xiaodong / Liu, Hang / Liu, Jinqing / Ly, Ngoc L. / Michell, Ashlin R. / Rassadkina, Yelizaveta / Seiger, Kyra / Sessa, Libera / Shin, Sally / Singh, Nishant / Sun, Weiwei / Sun, Xiaoming / Ticheli, Hannah J. / Waring, Michael T. / Zhu, Alex L. / Alter, Galit / Li, Jonathan Z. / Lingwood, Daniel / Schmidt, Aaron G. / Lichterfeld, Mathias / Walker, Bruce D. / Yu, Xu G. / Padera, Robert F. / Pillai, Shiv

Cell

2020 Volume 183, Issue 1, Page(s) 143–157.e13

Keywords	General Biochemistry, Genetics and Molecular Biology ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2020.08.025
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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