LIVIVO - Search results -

Search results

Result 1 - 10 of total 33

Search options

Article ; Online: Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18

Sayuri Miyauchi / Kei-ichiro Arimoto / Mengdan Liu / Yue Zhang / Dong-Er Zhang

Cell Reports, Vol 42, Iss 12, Pp 113560- (2023)

2023

Abstract: Summary: Tumor-associated myeloid cells modulate the tumor microenvironment and affect tumor progression. Type I interferon (IFN-I) has multiple effects on tumors and immune response, and ubiquitin-specific peptidase 18 (USP18) functions as a negative ... ...

Abstract	Summary: Tumor-associated myeloid cells modulate the tumor microenvironment and affect tumor progression. Type I interferon (IFN-I) has multiple effects on tumors and immune response, and ubiquitin-specific peptidase 18 (USP18) functions as a negative regulator of IFN-I signal transduction. This study aims to examine the function of IFN-I in myeloid cells during tumor progression. Here, we show that deletion of USP18 in myeloid cells suppresses tumor progression. Enhanced IFN-I signaling and blocked USP18 expression prompt downregulation of colony stimulating factor 1 receptor (CSF1R) and polarization of tumor-associated macrophages toward pro-inflammatory phenotypes. Further in vitro experiments reveal that downregulation of CSF1R is mediated by ubiquitin-proteasome degradation via E3 ligase neural precursor cell-expressed, developmentaly downregulated 4 (NEDD4) and the IFN-induced increase in ubiquitin E2 ubiquitin-conjugating enzyme H5. USP18 impairs ubiquitination and subsequent degradation of CSF1R by interrupting NEDD4 binding to CSF1R. These results reveal a previously unappreciated role of IFN-I in macrophage polarization by regulating CSF1R via USP18 and suggest targeting USP18 in myeloid-lineage cells as an effective strategy for IFN-based therapies.
Keywords	CP: Cancer ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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.

Article ; Online: Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18.

Miyauchi, Sayuri / Arimoto, Kei-Ichiro / Liu, Mengdan / Zhang, Yue / Zhang, Dong-Er

Cell reports

2023 Volume 42, Issue 12, Page(s) 113560

Abstract: Tumor-associated myeloid cells modulate the tumor microenvironment and affect tumor progression. Type I interferon (IFN-I) has multiple effects on tumors and immune response, and ubiquitin-specific peptidase 18 (USP18) functions as a negative regulator ... ...

Abstract	Tumor-associated myeloid cells modulate the tumor microenvironment and affect tumor progression. Type I interferon (IFN-I) has multiple effects on tumors and immune response, and ubiquitin-specific peptidase 18 (USP18) functions as a negative regulator of IFN-I signal transduction. This study aims to examine the function of IFN-I in myeloid cells during tumor progression. Here, we show that deletion of USP18 in myeloid cells suppresses tumor progression. Enhanced IFN-I signaling and blocked USP18 expression prompt downregulation of colony stimulating factor 1 receptor (CSF1R) and polarization of tumor-associated macrophages toward pro-inflammatory phenotypes. Further in vitro experiments reveal that downregulation of CSF1R is mediated by ubiquitin-proteasome degradation via E3 ligase neural precursor cell-expressed, developmentaly downregulated 4 (NEDD4) and the IFN-induced increase in ubiquitin E2 ubiquitin-conjugating enzyme H5. USP18 impairs ubiquitination and subsequent degradation of CSF1R by interrupting NEDD4 binding to CSF1R. These results reveal a previously unappreciated role of IFN-I in macrophage polarization by regulating CSF1R via USP18 and suggest targeting USP18 in myeloid-lineage cells as an effective strategy for IFN-based therapies.
MeSH term(s)	Tumor-Associated Macrophages ; Signal Transduction ; Receptor Protein-Tyrosine Kinases ; Ubiquitin ; Ubiquitination
Chemical Substances	Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Ubiquitin
Language	English
Publishing date	2023-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113560
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: RUNX1 C-terminal Mutations Impair Blood Cell Differentiation by Perturbing Specific Enhancer-Promoter Networks.

Jayne, Nathan Daniel / Liang, Zhengyu / Lim, Do-Hwan / Chen, Poshen Benson / Diaz, Cristina / Arimoto, Kei-Ichiro / Xia, Lingbo / Liu, Mengdan / Ren, Bing / Fu, Xiang-Dong / Zhang, Dong-Er

Blood advances

2024

Abstract: The transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not ... ...

Abstract	The transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not clearly understood how other RUNX1 mutations contribute to disease development. Here, we characterize RUNX1 mutations outside of the RHD. Our analysis of patient datasets revealed that mutations within the C-terminus frequently occur in hematopoietic disorders. Remarkably, most of these mutations were nonsense or frameshift and predicted to be exempt from nonsense mediated mRNA decay. Therefore, this class of mutation is projected to produce DNA-binding proteins that contribute to pathogenesis in a distinct manner. To model this, we introduced the RUNX1R320* mutation into the endogenous gene locus and demonstrated the production of RUNX1R320* protein. Expression of RUNX1R320* resulted in the disruption of RUNX1 regulated processes such as megakaryocytic differentiation through a transcriptional signature different from RUNX1 depletion. To understand the underlying mechanisms, we utilized Global RNA Interactions with DNA by deep sequencing (GRID-seq) to examine enhancer-promoter connections. We identified wide-spread alteration of enhancer-promoter networks within RUNX1 mutant cells. Additionally, we uncovered enrichment of RUNX1R320* and FOXK2 binding at the MYC super enhancer locus, significantly upregulating MYC transcription and signaling pathways. Together, our study demonstrates that most RUNX1 mutations outside the DNA binding domain are not subject to nonsense mediated decay, producing protein products that act in concert with additional cofactors to dysregulate hematopoiesis through mechanisms distinct from that induced by RUNX1 depletion.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023011484
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7153: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis.

Arimoto, Kei-Ichiro / Miyauchi, Sayuri / Troutman, Ty D / Zhang, Yue / Liu, Mengdan / Stoner, Samuel A / Davis, Amanda G / Fan, Jun-Bao / Huang, Yi-Jou / Yan, Ming / Glass, Christopher K / Zhang, Dong-Er

Nature communications

2023 Volume 14, Issue 1, Page(s) 251

Abstract: While immunotherapy has emerged as a breakthrough cancer therapy, it is only effective in some patients, indicating the need of alternative therapeutic strategies. Induction of cancer immunogenic cell death (ICD) is one promising way to elicit potent ... ...

Abstract	While immunotherapy has emerged as a breakthrough cancer therapy, it is only effective in some patients, indicating the need of alternative therapeutic strategies. Induction of cancer immunogenic cell death (ICD) is one promising way to elicit potent adaptive immune responses against tumor-associated antigens. Type I interferon (IFN) is well known to play important roles in different aspects of immune responses, including modulating ICD in anti-tumor action. However, how to expand IFN effect in promoting ICD responses has not been addressed. Here we show that depletion of ubiquitin specific protease 18 (USP18), a negative regulator of IFN signaling, selectively induces cancer cell ICD. Lower USP18 expression correlates with better survival across human selected cancer types and delays cancer progression in mouse models. Mechanistically, nuclear USP18 controls the enhancer landscape of cancer cells and diminishes STAT2-mediated transcription complex binding to IFN-responsive elements. Consequently, USP18 suppression not only enhances expression of canonical IFN-stimulated genes (ISGs), but also activates the expression of a set of atypical ISGs and NF-κB target genes, including genes such as Polo like kinase 2 (PLK2), that induce cancer pyroptosis. These findings may support the use of targeting USP18 as a potential cancer immunotherapy.
MeSH term(s)	Mice ; Animals ; Humans ; Pyroptosis ; Gene Pool ; Signal Transduction ; NF-kappa B/metabolism ; Interferon Type I/genetics ; Ubiquitin Thiolesterase/metabolism ; Neoplasms/genetics
Chemical Substances	NF-kappa B ; Interferon Type I ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; USP18 protein, human (EC 3.4.19.12)
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-35348-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Negative regulation of type I IFN signaling.

Arimoto, Kei-Ichiro / Miyauchi, Sayuri / Stoner, Samuel A / Fan, Jun-Bao / Zhang, Dong-Er

Journal of leukocyte biology

2018

Abstract: Type I IFNs (α, β, and others) are a family of cytokines that are produced in physiological conditions as well as in response to the activation of pattern recognition receptors. They are critically important in controlling the host innate and adaptive ... ...

Abstract	Type I IFNs (α, β, and others) are a family of cytokines that are produced in physiological conditions as well as in response to the activation of pattern recognition receptors. They are critically important in controlling the host innate and adaptive immune response to viral and some bacterial infections, cancer, and other inflammatory stimuli. However, dysregulation of type I IFN production or response can contribute to immune pathologies termed "interferonopathies", pointing to the importance of balanced activating signals with tightly regulated mechanisms of tuning this signaling. Here, we summarize the recent advances of how type I IFN production and response are controlled at multiple levels of the type I IFN signaling cascade.
Language	English
Publishing date	2018-01-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.2MIR0817-342R
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 603: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Plakophilin-2 induced EGFR phosphorylation: a focus on the intracellular activators of EGFR.

Arimoto, Kei-Ichiro / Weng, Stephanie / Zhang, Dong-Er

Receptors & clinical investigation

2015 Volume 2, Issue 1, Page(s) e485

Abstract: The oncogenic role of EGFR in many tumors has attracted a great deal of attention in the recent years and initiated the development of several potent EGFR inhibitors, which are used clinically for cancer treatment. However, the current therapeutic ... ...

Abstract	The oncogenic role of EGFR in many tumors has attracted a great deal of attention in the recent years and initiated the development of several potent EGFR inhibitors, which are used clinically for cancer treatment. However, the current therapeutic inhibition of EGFR signaling is limited to monoclonal antibodies that bind to the EGFR extracellular domain or tyrosine kinase inhibitors that block EGFR kinase activation directly. Despite the great promise of these inhibitors, a certain percentage of patients develop resistance to these therapies, highlighting the necessity for alternative therapeutic strategies based on our most current knowledge of the mechanisms of EGFR signaling. We recently reported that Plakofilin-2 (PKP2) is a novel ligand-independent cytoplasmic activator of EGFR signaling. Here we focus on recent studies demonstrating important roles of intracellular EGFR activators, and propose targeted disruption of these activators as a novel avenue of therapeutic intervention to inhibit EGFR-mediated cancer development.
Language	English
Publishing date	2015-05-21
Publishing country	United States
Document type	Journal Article
ISSN	2330-0558
ISSN	2330-0558
DOI	10.14800/rci.485
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

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.

Article ; Online: Cell-cycle-gated feedback control mediates desensitization to interferon stimulation.

Mudla, Anusorn / Jiang, Yanfei / Arimoto, Kei-Ichiro / Xu, Bingxian / Rajesh, Adarsh / Ryan, Andy P / Wang, Wei / Daugherty, Matthew D / Zhang, Dong-Er / Hao, Nan

eLife

2020 Volume 9

Abstract: Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational ... ...

Abstract	Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive regulatory network operates in single human cells to process repetitive IFN stimulation. We found that IFN-α pretreatments lead to opposite effects, priming versus desensitization, depending on input durations. These effects are governed by a regulatory network composed of a fast-acting positive feedback loop and a delayed negative feedback loop, mediated by upregulation of ubiquitin-specific peptidase 18 (USP18). We further revealed that USP18 upregulation can only be initiated at the G1/early S phases of cell cycle upon the treatment onset, resulting in heterogeneous and delayed induction kinetics in single cells. This cell cycle gating provides a temporal compartmentalization of feedback loops, enabling duration-dependent desensitization to repetitive stimulations.
MeSH term(s)	Cell Cycle/drug effects ; Cell Cycle/physiology ; Feedback, Physiological/drug effects ; Feedback, Physiological/physiology ; HEK293 Cells ; HeLa Cells ; Humans ; Interferon-alpha/metabolism ; Interferon-alpha/pharmacology ; Kinetics ; Single-Cell Analysis ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism ; Up-Regulation
Chemical Substances	Interferon-alpha ; USP18 protein, human (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Keywords	covid19
Language	English
Publishing date	2020-09-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.58825
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Cell-cycle-gated feedback control mediates desensitization to interferon stimulation

Anusorn Mudla / Yanfei Jiang / Kei-ichiro Arimoto / Bingxian Xu / Adarsh Rajesh / Andy P Ryan / Wei Wang / Matthew D Daugherty / Dong-Er Zhang / Nan Hao

eLife, Vol

2020 Volume 9

Abstract	Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive regulatory network operates in single human cells to process repetitive IFN stimulation. We found that IFN-α pretreatments lead to opposite effects, priming versus desensitization, depending on input durations. These effects are governed by a regulatory network composed of a fast-acting positive feedback loop and a delayed negative feedback loop, mediated by upregulation of ubiquitin-specific peptidase 18 (USP18). We further revealed that USP18 upregulation can only be initiated at the G1/early S phases of cell cycle upon the treatment onset, resulting in heterogeneous and delayed induction kinetics in single cells. This cell cycle gating provides a temporal compartmentalization of feedback loops, enabling duration-dependent desensitization to repetitive stimulations.
Keywords	interferons ; desensitization ; signal dynamics ; single-cell analysis ; time-lapse microscopy ; computational modeling ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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.

Article: Regulation of viral recognition signaling by ubiquitin modification.

Arimoto, Kei-ichiro / Shimotohno, Kunitada

Uirusu

2008 Volume 58, Issue 1, Page(s) 47–54

Abstract: As a defense mechanism against infection, host cells have evolved sensor molecules which detect pathogen components directly and induce protective responses against the infection. TLRs, well known receptors, recognize a pathogen on the surface of cells ... ...

Abstract	As a defense mechanism against infection, host cells have evolved sensor molecules which detect pathogen components directly and induce protective responses against the infection. TLRs, well known receptors, recognize a pathogen on the surface of cells or endosome/lysosome. Many pathogens penetrate into cytoplasm, in where non-TLR sensors recognize pathogen components including double-stranded RNA (dsRNA). On the downstream of each sensor, a variety of functional signaling molecules are activated to produce various cytokines upon the microbial invasion to induce host defense responses. Because that cytokines produced to regulate the host defense responses are known to affect cell proliferation also, the level of these molecules are needed to be controlled tightly, which means requisites of negative regulation of the signaling activated by pathogen after the completion of proper immune responses. Recent studies suggest important roles of some ubiquitin systems in this regulation. Here we focus, in particular, ubiquitin conjugation to signaling molecules by virus activation and like to show how ubiquitin signaling plays roles in this regulation by introducing some recent works.
MeSH term(s)	Animals ; Cytokines/physiology ; Humans ; Protein Sorting Signals/physiology ; RNA, Double-Stranded/immunology ; Signal Transduction/immunology ; Signal Transduction/physiology ; Toll-Like Receptors/immunology ; Ubiquitin/metabolism ; Ubiquitin/physiology ; Ubiquitination/physiology ; Virus Activation ; Viruses/immunology
Chemical Substances	Cytokines ; Protein Sorting Signals ; RNA, Double-Stranded ; Toll-Like Receptors ; Ubiquitin
Language	English
Publishing date	2008-12-31
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	603272-2
ISSN	0042-6857
ISSN	0042-6857
DOI	10.2222/jsv.58.47
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 266: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling.

Stoner, Samuel A / Liu, Katherine Tin Heng / Andrews, Elizabeth T / Liu, Mengdan / Arimoto, Kei-Ichiro / Yan, Ming / Davis, Amanda G / Weng, Stephanie / Dow, Michelle / Xian, Su / DeKelver, Russell C / Carter, Hannah / Zhang, Dong-Er

Blood cancer journal

2020 Volume 10, Issue 2, Page(s) 16

Abstract: Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal ...

Abstract	Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal gene expression. Despite this knowledge, the specific gene expression alterations that contribute to the development of leukemia remain incompletely understood. Here, through characterization of transcriptional regulation by the RUNX1-ETO fusion protein, we have identified Ras-association domain family member 2 (RASSF2) as a critical gene that is aberrantly transcriptionally repressed in t(8;21)-associated AML. Re-expression of RASSF2 specifically inhibits t(8;21) AML development in multiple models. Through biochemical and functional studies, we demonstrate RASSF2-mediated functions to be dependent on interaction with Hippo kinases, MST1 and MST2, but independent of canonical Hippo pathway signaling. Using proximity-based biotin labeling we define the RASSF2-proximal proteome in leukemia cells and reveal association with Rac GTPase-related proteins, including an interaction with the guanine nucleotide exchange factor, DOCK2. Importantly, RASSF2 knockdown impairs Rac GTPase activation, and RASSF2 expression is broadly correlated with Rac-mediated signal transduction in AML patients. Together, these data reveal a previously unappreciated mechanistic link between RASSF2, Hippo kinases, and Rac activity with potentially broad functional consequences in leukemia.
MeSH term(s)	Animals ; Biomarkers, Tumor/genetics ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Human, Pair 8/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/prevention & control ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Translocation, Genetic ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Xenograft Model Antitumor Assays ; rac GTP-Binding Proteins/genetics ; rac GTP-Binding Proteins/metabolism
Chemical Substances	Biomarkers, Tumor ; Oncogene Proteins, Fusion ; RASSF2 protein, human ; RUNX1-IT1 long non-coding RNA, human ; Tumor Suppressor Proteins ; rac GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2020-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-020-0282-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito