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Article ; Online: A SNP of lncRNA gives HIV-1 a boost.

Janaka, Sanath Kumar / Evans, David T

2019 Volume 20, Issue 7, Page(s) 778–780

MeSH term(s)	HIV Infections ; HIV-1/genetics ; Humans ; RNA, Long Noncoding/genetics ; Receptors, CCR5
Chemical Substances	CCR5 protein, human ; RNA, Long Noncoding ; Receptors, CCR5
Language	English
Publishing date	2019-06-18
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-019-0422-1
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Article ; Online: Substitutions in Nef That Uncouple Tetherin and SERINC5 Antagonism Impair Simian Immunodeficiency Virus Replication in Primary Rhesus Macaque Lymphocytes.

Janaka, Sanath Kumar / Snow, Brian J / Behrens, Ryan T / Evans, David T

Journal of virology

2022 Volume 96, Issue 11, Page(s) e0017622

Abstract: Most simian immunodeficiency viruses (SIVs) use Nef to counteract restriction by the tetherin proteins of their nonhuman primate hosts. In addition to counteracting tetherin, SIV Nef has a number of other functions, including the downmodulation of CD3, ... ...

Abstract	Most simian immunodeficiency viruses (SIVs) use Nef to counteract restriction by the tetherin proteins of their nonhuman primate hosts. In addition to counteracting tetherin, SIV Nef has a number of other functions, including the downmodulation of CD3, CD4, and major histocompatibility complex class I (MHC I) molecules from the surface of SIV-infected cells and the enhancement of viral infectivity by preventing the incorporation of SERINC5 into virions. Although these activities require different surfaces of Nef, they can be difficult to separate because of their dependence on similar interactions with AP-1 or AP-2 for clathrin-mediated endocytosis. We previously observed extensive overlap of the SIV Nef residues required for counteracting tetherin and SERINC5. Here, we define substitutions in Nef that separate anti-tetherin activity from SERINC5 antagonism and other activities of Nef. This information was used to engineer an infectious molecular clone of SIV (SIV
MeSH term(s)	Animals ; Bone Marrow Stromal Antigen 2/metabolism ; CD4-Positive T-Lymphocytes ; Gene Products, nef/genetics ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Interferons/metabolism ; Lymphocytes/metabolism ; Lymphocytes/virology ; Macaca mulatta ; Membrane Proteins/metabolism ; Simian Immunodeficiency Virus/physiology ; Virus Replication
Chemical Substances	Bone Marrow Stromal Antigen 2 ; Gene Products, nef ; Histocompatibility Antigens Class I ; Membrane Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2022-05-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00176-22
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Article: Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay.

Janaka, Sanath Kumar / Clark, Natasha M / Evans, David T / Connor, Joseph P

medRxiv : the preprint server for health sciences

2021

Abstract: Background: The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic ... ...

Abstract	Background: The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. Study design and methods: Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). Results: All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. Discussion: Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.
Language	English
Publishing date	2021-03-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.08.21253135
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Article ; Online: The Antiviral Factor SERINC5 Impairs the Expression of Non-Self-DNA.

Shi, Yuhang / Simpson, Sydney / Ahmed, Shahad K / Chen, Yuexuan / Tavakoli-Tameh, Aidin / Janaka, Sanath Kumar / Evans, David T / Serra-Moreno, Ruth

Viruses

2023 Volume 15, Issue 9

Abstract: SERINC5 is a restriction factor that becomes incorporated into nascent retroviral particles, impairing their ability to infect target cells. In turn, retroviruses have evolved countermeasures against SERINC5. For instance, the primate lentiviruses (HIV ... ...

Abstract	SERINC5 is a restriction factor that becomes incorporated into nascent retroviral particles, impairing their ability to infect target cells. In turn, retroviruses have evolved countermeasures against SERINC5. For instance, the primate lentiviruses (HIV and SIV) use Nef, Moloney Murine Leukemia Virus (MLV) uses GlycoGag, and Equine Infectious Anemia Virus (EIAV) uses S2 to remove SERINC5 from the plasma membrane, preventing its incorporation into progeny virions. Recent studies have shown that SERINC5 also restricts other viruses, such as Hepatitis B Virus (HBV) and Classical Swine Fever Virus (CSFV), although through a different mechanism, suggesting that SERINC5 can interfere with multiple stages of the virus life cycle. To investigate whether SERINC5 can also impact other steps of the replication cycle of HIV, the effects of SERINC5 on viral transcripts, proteins, and virus progeny size were studied. Here, we report that SERINC5 causes significant defects in HIV gene expression, which impacts virion production. While the underlying mechanism is still unknown, we found that the restriction occurs at the transcriptional level and similarly affects plasmid and non-integrated proviral DNA (ectopic or non-self-DNA). However, SERINC5 causes no defects in the expression of viral RNA, host genes, or proviral DNA that is integrated in the cellular genome. Hence, our findings reveal that SERINC5's actions in host defense extend beyond blocking virus entry.
MeSH term(s)	Animals ; Swine ; Horses ; Mice ; Antiviral Agents ; DNA ; Cell Membrane ; Classical Swine Fever Virus ; Proviruses ; Retroviridae ; HIV Infections
Chemical Substances	Antiviral Agents ; DNA (9007-49-2)
Language	English
Publishing date	2023-09-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15091961
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Article ; Online: Selective Disruption of SERINC5 Antagonism by Nef Impairs SIV Replication in Primary CD4

Janaka, Sanath Kumar / Palumbo, Alexandra V / Tavakoli-Tameh, Aidin / Evans, David T

Journal of virology

2021 Volume 95, Issue 8

Abstract: The Nef proteins of HIV-1 and SIV enhance viral infectivity by preventing the incorporation of the multipass transmembrane protein serine incorporator 5 (SERINC5), and to a lesser extent SERINC3, into virions. In addition to counteracting SERINCs, SIV ... ...

Abstract	The Nef proteins of HIV-1 and SIV enhance viral infectivity by preventing the incorporation of the multipass transmembrane protein serine incorporator 5 (SERINC5), and to a lesser extent SERINC3, into virions. In addition to counteracting SERINCs, SIV Nef also downmodulates several transmembrane proteins from the surface of virus-infected cells, including simian tetherin, CD4 and MHC class I (MHC I) molecules. From a systematic analysis of alanine substitutions throughout the SIV
Language	English
Publishing date	2021-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01911-20
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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Predicting the efficacy of COVID-19 convalescent plasma donor units with the Lumit Dx anti-receptor binding domain assay.

Janaka, Sanath Kumar / Clark, Natasha M / Evans, David T / Mou, Huihui / Farzan, Michael / Connor, Joseph P

PloS one

2021 Volume 16, Issue 7, Page(s) e0253551

Abstract	Background: The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. Study design and methods: Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). Results: All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. Discussion: Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/immunology ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Blood Donors ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/therapy ; COVID-19/virology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immune Sera/chemistry ; Immunization, Passive/methods ; Immunoglobulin G/blood ; Neutralization Tests ; Predictive Value of Tests ; Protein Binding ; Protein Domains ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; COVID-19 Serotherapy
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immune Sera ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0253551
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Article ; Online: KIR3DL05 and KIR3DS02 Recognition of a Nonclassical MHC Class I Molecule in the Rhesus Macaque Implicated in Pregnancy Success.

Nicholas, Rachel E / Sandstrom, Kjell / Anderson, Jennifer L / Smith, Willow R / Wetzel, Molly / Banerjee, Priyankana / Janaka, Sanath Kumar / Evans, David T

Frontiers in immunology

2022 Volume 13, Page(s) 841136

Abstract: Knowledge of the MHC class I ligands of rhesus macaque killer-cell Ig-like receptors (KIRs) is fundamental to understanding the role of natural killer (NK) cells in this species as a nonhuman primate model for infectious diseases, transplantation and ... ...

Abstract	Knowledge of the MHC class I ligands of rhesus macaque killer-cell Ig-like receptors (KIRs) is fundamental to understanding the role of natural killer (NK) cells in this species as a nonhuman primate model for infectious diseases, transplantation and reproductive biology. We previously identified Mamu-AG as a ligand for KIR3DL05. Mamu-AG is a nonclassical MHC class I molecule that is expressed at the maternal-fetal interface of the placenta in rhesus macaques similar to HLA-G in humans. Although Mamu-AG and HLA-G share similar molecular features, including limited polymorphism and a short cytoplasmic tail, Mamu-AG is considerably more polymorphic. To determine which allotypes of Mamu-AG serve as ligands for KIR3DL05, we tested reporter cell lines expressing five different alleles of KIR3DL05 (KIR3DL05001, KIR3DL05004, KIR3DL05005, KIR3DL05008 and KIR3DL05X) for responses to target cells expressing eight different alleles of Mamu-AG. All five allotypes of KIR3DL05 responded to Mamu-AG201:01, two exhibited dominant responses to Mamu-AG105:01, and three had low but detectable responses to Mamu-AG303:01, -AG303:02, -AG303:03 and -AG303:04. Since KIR3DL05X is the product of recombination between
MeSH term(s)	Animals ; Female ; Genes, MHC Class I ; HLA-G Antigens ; Ligands ; Macaca mulatta ; Pregnancy ; Receptors, KIR/genetics
Chemical Substances	HLA-G Antigens ; Ligands ; Receptors, KIR
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.841136
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Article ; Online: Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

Natasha M. Clark / Sanath Kumar Janaka / William Hartman / Susan Stramer / Erin Goodhue / John Weiss / David T. Evans / Joseph P. Connor

PLoS ONE, Vol 17, Iss

2022 Volume 3

Abstract: The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the ... ...

Abstract	The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection.

Natasha M Clark / Sanath Kumar Janaka / William Hartman / Susan Stramer / Erin Goodhue / John Weiss / David T Evans / Joseph P Connor

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0257930

Abstract	The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection.

Clark, Natasha M / Janaka, Sanath Kumar / Hartman, William / Stramer, Susan / Goodhue, Erin / Weiss, John / Evans, David T / Connor, Joseph P

PloS one

2022 Volume 17, Issue 3, Page(s) e0257930

Abstract	The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibodies, Viral/therapeutic use ; COVID-19/therapy ; COVID-19/virology ; Female ; HEK293 Cells ; Humans ; Immunization, Passive ; Immunoglobulin A/blood ; Immunoglobulin A/immunology ; Immunoglobulin A/therapeutic use ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunoglobulin G/therapeutic use ; Male ; Middle Aged ; Neutralization Tests ; Receptors, IgG/genetics ; Receptors, IgG/metabolism ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult ; COVID-19 Serotherapy
Chemical Substances	Antibodies, Viral ; Fc gamma receptor IIA ; Immunoglobulin A ; Immunoglobulin G ; Receptors, IgG ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0257930
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