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Article ; Online: Structural heterogeneity of the mammalian polycomb repressor complex in immune regulation.

Kang, Seok-Jin / Chun, Taehoon

2020 Volume 52, Issue 7, Page(s) 1004–1015

Abstract: Epigenetic regulation is mainly mediated by enzymes that can modify the structure of chromatin by altering the structure of DNA or histones. Proteins involved in epigenetic processes have been identified to study the detailed molecular mechanisms ... ...

Abstract	Epigenetic regulation is mainly mediated by enzymes that can modify the structure of chromatin by altering the structure of DNA or histones. Proteins involved in epigenetic processes have been identified to study the detailed molecular mechanisms involved in the regulation of specific mRNA expression. Evolutionarily well-conserved polycomb group (PcG) proteins can function as transcriptional repressors by the trimethylation of histone H3 at the lysine 27 residue (H3K27me3) and the monoubiquitination of histone H2A at the lysine 119 residue (H2AK119ub). PcG proteins form two functionally distinct protein complexes: polycomb repressor complex 1 (PRC1) and PRC2. In mammals, the structural heterogeneity of each PRC complex is dramatically increased by several paralogs of its subunit proteins. Genetic studies with transgenic mice along with RNA-seq and chromatin immunoprecipitation (ChIP)-seq analyses might be helpful for defining the cell-specific functions of paralogs of PcG proteins. Here, we summarize current knowledge about the immune regulatory role of PcG proteins related to the compositional diversity of each PRC complex and introduce therapeutic drugs that target PcG proteins in hematopoietic malignancy.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Hematologic Neoplasms/pathology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; Immunity ; Mammals/immunology ; Polycomb Repressive Complex 1/antagonists & inhibitors ; Polycomb Repressive Complex 1/chemistry ; Polycomb Repressive Complex 1/metabolism
Chemical Substances	Polycomb Repressive Complex 1 (EC 2.3.2.27)
Language	English
Publishing date	2020-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-020-0462-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein (NSP)1 transcriptionally inhibits CCN1 and CCN2 expression by blocking ERK-AP-1 axis in pig macrophages in vitro.

Park, In-Byung / Chun, Taehoon

Research in veterinary science

2020 Volume 132, Page(s) 462–465

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS that has generated a serious adverse impact on current global pork production. PRRSV primarily infects pig alveolar macrophages, but poor induction of innate ... ...

Abstract	Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS that has generated a serious adverse impact on current global pork production. PRRSV primarily infects pig alveolar macrophages, but poor induction of innate immunity after infection often leads to more severe complications. Defining the functional role of each PRRSV non structural protein (NSP) within host cells might be helpful in understanding how PRRSV induces poor innate immunity in host cells. NSP1 of PRRSV exhibits papain like cysteine protease activity and may therefore modulate host cell signaling by degrading a target protein in host cells during infection. In this study, we demonstrated that NSP1 of PRRSV-2 indirectly blocked extracellular signal-regulated kinase (ERK) signaling in polyriboinosinic polyribocytidylic acid (Poly I:C) stimulated pig macrophages (3D4/31 cells). ERK which belongs to the mitogen-activated protein kinase family mediates many biological processes including inflammatory responses during viral infection. The blocking of ERK signaling by NSP1 of PRRSV-2 further leads to the transcriptional inhibition of inflammatory enhancers, cellular communication network factor 1 and 2 (ccn1 and ccn2) through down-regulation of v-fos FBJ murine osteosarcoma viral oncogene homolog (fos) and fosb, the component of activating protein-1 (AP-1) which is an ERK downstream transcription factor. Therefore, NSP1 of PRRSV-2 inhibited the mRNA transcription of ccn1 and ccn2 by blocking the ERK-AP-1 axis in Poly I:C stimulated pig macrophages. These results provide additional evidence supporting that NSP1 has anti-inflammatory function during PRRSV-2 infection.
MeSH term(s)	Animals ; Cell Line ; Connective Tissue Growth Factor/genetics ; Connective Tissue Growth Factor/metabolism ; Cysteine-Rich Protein 61/genetics ; Cysteine-Rich Protein 61/metabolism ; Down-Regulation ; Immunity, Innate ; Macrophages ; Macrophages, Alveolar ; Mice ; Porcine respiratory and reproductive syndrome virus ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Signal Transduction ; Swine ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Cysteine-Rich Protein 61 ; RNA, Messenger ; Transcription Factor AP-1 ; Viral Nonstructural Proteins ; Connective Tissue Growth Factor (139568-91-5)
Language	English
Publishing date	2020-08-05
Publishing country	England
Document type	Journal Article
ZDB-ID	840961-4
ISSN	1532-2661 ; 0034-5288
ISSN (online)	1532-2661
ISSN	0034-5288
DOI	10.1016/j.rvsc.2020.07.029
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Article: Porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein (NSP)1 transcriptionally inhibits CCN1 and CCN2 expression by blocking ERK-AP-1 axis in pig macrophages in vitro

Park, In-Byung / Chun, Taehoon

Research in veterinary science. 2020 Oct., v. 132

2020

Abstract	Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS that has generated a serious adverse impact on current global pork production. PRRSV primarily infects pig alveolar macrophages, but poor induction of innate immunity after infection often leads to more severe complications. Defining the functional role of each PRRSV non structural protein (NSP) within host cells might be helpful in understanding how PRRSV induces poor innate immunity in host cells. NSP1 of PRRSV exhibits papain like cysteine protease activity and may therefore modulate host cell signaling by degrading a target protein in host cells during infection. In this study, we demonstrated that NSP1 of PRRSV-2 indirectly blocked extracellular signal-regulated kinase (ERK) signaling in polyriboinosinic polyribocytidylic acid (Poly I:C) stimulated pig macrophages (3D4/31 cells). ERK which belongs to the mitogen-activated protein kinase family mediates many biological processes including inflammatory responses during viral infection. The blocking of ERK signaling by NSP1 of PRRSV-2 further leads to the transcriptional inhibition of inflammatory enhancers, cellular communication network factor 1 and 2 (ccn1 and ccn2) through down-regulation of v-fos FBJ murine osteosarcoma viral oncogene homolog (fos) and fosb, the component of activating protein-1 (AP-1) which is an ERK downstream transcription factor. Therefore, NSP1 of PRRSV-2 inhibited the mRNA transcription of ccn1 and ccn2 by blocking the ERK-AP-1 axis in Poly I:C stimulated pig macrophages. These results provide additional evidence supporting that NSP1 has anti-inflammatory function during PRRSV-2 infection.
Keywords	Betaarterivirus suid 2 ; enzyme activity ; innate immunity ; macrophages ; mice ; mitogen-activated protein kinase ; oncogenes ; osteosarcoma ; papain ; pathogens ; polyinosinic-polycytidylic acid ; porcine reproductive and respiratory syndrome ; pork ; research ; structural proteins ; swine ; transcription (genetics) ; transcription factors ; veterinary medicine ; viral nonstructural proteins ; viruses
Language	English
Dates of publication	2020-10
Size	p. 462-465.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	840961-4
ISSN	1532-2661 ; 0034-5288
ISSN (online)	1532-2661
ISSN	0034-5288
DOI	10.1016/j.rvsc.2020.07.029
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Open reading frame 5 protein of porcine circovirus type 2 induces RNF128 (GRAIL) which inhibits mRNA transcription of interferon-β in porcine epithelial cells.

Kang, Seok-Jin / Park, In-Byung / Chun, Taehoon

Research in veterinary science

2021 Volume 140, Page(s) 79–82

Abstract: A previous study has indicated that mRNA transcript of Rnf128 (Grail) is significantly increased in porcine epithelial cells expressing porcine circovirus type 2 (PCV2) open reading frame 5 (ORF5). RNF128 is an E3 ubiquitin ligase that can modulate the ... ...

Abstract	A previous study has indicated that mRNA transcript of Rnf128 (Grail) is significantly increased in porcine epithelial cells expressing porcine circovirus type 2 (PCV2) open reading frame 5 (ORF5). RNF128 is an E3 ubiquitin ligase that can modulate the activity of target protein via ubiquitination of specific lysine residues. However, the function of RNF128 in PCV2-infected epithelial cells has not been well studied yet. Thus, the objective of the present study was to examine the functional role of RNF128 in porcine epithelial cells (PK15 cells) after PCV2 infection. Results clearly indicated that PCV2 ORF5 increased the expression of RNF128 which inhibited type I IFN production and enhanced viral replication of PCV2 in PK15 cells. Therefore, up-regulating RNF128 by PCV2 ORF5 can help PCV2 circumvent initial immune surveillance of porcine epithelial cells.
MeSH term(s)	Animals ; Cell Line ; Circoviridae Infections/veterinary ; Circovirus/genetics ; Epithelial Cells ; Interferons ; Open Reading Frames ; RNA, Messenger/genetics ; Swine ; Swine Diseases ; Virus Replication
Chemical Substances	RNA, Messenger ; Interferons (9008-11-1)
Language	English
Publishing date	2021-08-13
Publishing country	England
Document type	Journal Article
ZDB-ID	840961-4
ISSN	1532-2661 ; 0034-5288
ISSN (online)	1532-2661
ISSN	0034-5288
DOI	10.1016/j.rvsc.2021.08.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Interaction between host cell proteins and open reading frames of porcine circovirus type 2.

Park, Si-Won / Park, In-Byung / Kang, Seok-Jin / Bae, Joonbeom / Chun, Taehoon

Journal of animal science and technology

2023 Volume 65, Issue 4, Page(s) 698–719

Abstract: Postweaning multisystemic wasting syndrome (PMWS) is caused by a systemic inflammation after porcine circovirus type 2 (PCV2) infection. It was one of the most economically important pathogens affecting pig production worldwide before PCV2 vaccine was ... ...

Abstract	Postweaning multisystemic wasting syndrome (PMWS) is caused by a systemic inflammation after porcine circovirus type 2 (PCV2) infection. It was one of the most economically important pathogens affecting pig production worldwide before PCV2 vaccine was first introduced in 2006. After the development of a vaccine against PCV2a type, pig farms gradually restored enormous economic losses from PMWS. However, vaccine against PCV2a type could not be fully effective against several different PCV2 genotypes (PCV2b - PCV2h). In addition, PCV2a vaccine itself could generate antigenic drift of PCV2 capsid. Therefore, PCV2 infection still threats pig industry worldwide. PCV2 infection was initially found in local tissues including reproductive, respiratory, and digestive tracks. However, PCV2 infection often leads to a systemic inflammation which can cause severe immunosuppression by depleting peripheral lymphocytes in secondary lymphoid tissues. Subsequently, a secondary infection with other microorganisms can cause PMWS. Eleven putative open reading frames (ORFs) have been predicted to encode PCV2 genome. Among them, gene products of six ORFs from ORF1 to ORF6 have been identified and characterized to estimate its functional role during PCV2 infection. Acquiring knowledge about the specific interaction between each PCV2 ORF protein and host protein might be a key to develop preventive or therapeutic tools to control PCV2 infection. In this article, we reviewed current understanding of how each ORF of PCV2 manipulates host cell signaling related to immune suppression caused by PCV2.
Language	English
Publishing date	2023-07-30
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2775231-8
ISSN	2055-0391
ISSN	2055-0391
DOI	10.5187/jast.2023.e67
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Article ; Online: Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function.

Lee, Chang-Hee / Chun, Taehoon

Molecules and cells

2019 Volume 42, Issue 1, Page(s) 1–7

Abstract: Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, ...

Abstract	Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/metabolism ; Apoptosis ; Humans ; Inflammasomes/metabolism ; Ligands ; Macrophages/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Inflammasomes ; Ligands ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2019-01-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2018.0419
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Article: Open reading frame 5 protein of porcine circovirus type 2 induces RNF128 (GRAIL) which inhibits mRNA transcription of interferon-β in porcine epithelial cells

Kang, Seok-Jin / Park, In-Byung / Chun, Taehoon

Research in veterinary science. 2021 Nov., v. 140

2021

Abstract	A previous study has indicated that mRNA transcript of Rnf128 (Grail) is significantly increased in porcine epithelial cells expressing porcine circovirus type 2 (PCV2) open reading frame 5 (ORF5). RNF128 is an E3 ubiquitin ligase that can modulate the activity of target protein via ubiquitination of specific lysine residues. However, the function of RNF128 in PCV2-infected epithelial cells has not been well studied yet. Thus, the objective of the present study was to examine the functional role of RNF128 in porcine epithelial cells (PK15 cells) after PCV2 infection. Results clearly indicated that PCV2 ORF5 increased the expression of RNF128 which inhibited type I IFN production and enhanced viral replication of PCV2 in PK15 cells. Therefore, up-regulating RNF128 by PCV2 ORF5 can help PCV2 circumvent initial immune surveillance of porcine epithelial cells.
Keywords	Porcine circovirus-2 ; epithelium ; lysine ; monitoring ; research ; swine ; ubiquitin-protein ligase ; ubiquitination ; veterinary medicine ; virus replication
Language	English
Dates of publication	2021-11
Size	p. 79-82.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	840961-4
ISSN	1532-2661 ; 0034-5288
ISSN (online)	1532-2661
ISSN	0034-5288
DOI	10.1016/j.rvsc.2021.08.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Monitoring mRNA Expression Patterns in Macrophages in Response to Two Different Strains of Probiotics.

Choi, Sang-Pil / Park, Si-Won / Kang, Seok-Jin / Lim, Seul Ki / Kwon, Min-Sung / Choi, Hak-Jong / Chun, Taehoon

Food science of animal resources

2023 Volume 43, Issue 4, Page(s) 703–711

Abstract: As an initial study to elucidate the molecular mechanism of how probiotics modulate macrophage activity, we monitored mRNA expression patterns in peritoneal macrophages (PMs) treated with two different strains of probiotics. After treatment with ... ...

Abstract	As an initial study to elucidate the molecular mechanism of how probiotics modulate macrophage activity, we monitored mRNA expression patterns in peritoneal macrophages (PMs) treated with two different strains of probiotics. After treatment with either
Language	English
Publishing date	2023-07-01
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	3016289-0
ISSN	2636-0780 ; 2636-0772
ISSN (online)	2636-0780
ISSN	2636-0772
DOI	10.5851/kosfa.2023.e23
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Article: Expression of Major Histocompatibility Complex during Neuronal Differentiation of Somatic Cell Nuclear Transfer-Human Embryonic Stem Cells.

Lee, Jin Saem / Lee, Jeoung Eun / Yu, Shin-Hye / Chun, Taehoon / Chang, Mi-Yoon / Lee, Dong Ryul / Park, Chang-Hwan

International journal of stem cells

2023 Volume 17, Issue 1, Page(s) 59–69

Abstract: Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of ... ...

Abstract	Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured
Language	English
Publishing date	2023-10-26
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2914134-5
ISSN	2005-5447 ; 2005-3606
ISSN (online)	2005-5447
ISSN	2005-3606
DOI	10.15283/ijsc23037
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Article: Transcriptome analysis of pig macrophages expressing porcine reproductive and respiratory syndrome virus non-structural protein 1

Park, In-Byung / Choi, Yong-Chan / Lee, Kyung-Tai / Chun, Taehoon

Veterinary immunology and immunopathology. 2021 Jan., v. 231

2021

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS, one of the most economically disastrous swine diseases. Non-structural protein 1 (NSP1) of PRRSV consists of NSP1α and NSP1β which exhibit papain like cysteine ... ...

Abstract	Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS, one of the most economically disastrous swine diseases. Non-structural protein 1 (NSP1) of PRRSV consists of NSP1α and NSP1β which exhibit papain like cysteine protease activity. Recent evidence demonstrates that PRRSV NSP1 may be participated in modulating host immunity, but very few host proteins were discovered as targets for NSP1. In this study, we used RNA-seq to investigate the functional role of PRRSV NSP1 in porcine alveolar macrophages, 3D4/31 cells. Compared to empty vector (mock) transfectant, NSP1, NSP1α, and NSP1β expressing 3D4/31 cells displayed a total of 60 genes, 63 genes, and 80 genes as differentially expressed genes (DEGs), respectively. Most of DEGs are involved in early inflammatory responses including interleukin (IL)-17 signaling pathway, chemokine signaling pathway, tumor necrosis factor (TNF)-α signaling pathway, and cell adhesion molecules. Interestingly, PRRSV NSP1 expression in 3D4/31 cells decreased mRNA transcripts of Fosb and Gdf15 known to be involved in host cell signaling or host cell protection during inflammation. Therefore, PRRSV NSP1 might block the signaling involved in host immune surveillance. Further study is required to define the mechanism on how PRRSV NSP1 protein represses mRNA transcripts of specific host genes.
Keywords	cell adhesion ; chemokines ; enzyme activity ; gene expression regulation ; immunity ; immunopathology ; inflammation ; macrophages ; monitoring ; papain ; pathogens ; porcine reproductive and respiratory syndrome ; sequence analysis ; swine ; transcriptomics ; viral nonstructural proteins ; viruses
Language	English
Dates of publication	2021-01
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2020.110147
Database	NAL-Catalogue (AGRICOLA)

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