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Article ; Online: Self-assembly of DNA parallel double-crossover motifs.

Lee, Jung Yeon / Yang, Qi / Chang, Xu / Jeziorek, Maciej / Perumal, Devanathan / Olivera, Tiffany R / Etchegaray, Jean-Pierre / Zhang, Fei

Nanoscale

2024 Volume 16, Issue 4, Page(s) 1685–1691

Abstract: DNA double-crossover motifs, including parallel and antiparallel crossovers, serve as the structural foundation for the creation of diverse nanostructures and dynamic devices in DNA nanotechnology. Parallel crossover motifs have unique advantages over ... ...

Abstract	DNA double-crossover motifs, including parallel and antiparallel crossovers, serve as the structural foundation for the creation of diverse nanostructures and dynamic devices in DNA nanotechnology. Parallel crossover motifs have unique advantages over the widely used antiparallel crossover design but have not developed as substantially due to the difficulties in assembly. Here we created 29 designs of parallel double-crossover motifs varying in hybridization pathways, central domain lengths, and crossover locations to investigate their assembly mechanism. Arrays were successfully formed in four distinct designs, and large tubular structures were obtained in seven designs with predefined pathways and central domains appoximately 16 nucleotides in length. The nanotubes obtained from parallel crossover design showed improved nuclease resistance than the ones from the antiparallel counterpart design. Overall, our study provides a basis for the development of generalized assembly rules of DNA parallel crossover systems and opens new opportunities for their potential use in biological systems.
MeSH term(s)	Nucleic Acid Conformation ; DNA/chemistry ; Nanotechnology ; Nanostructures/chemistry ; Nanotubes/chemistry
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2515664-0
ISSN	2040-3372 ; 2040-3364
ISSN (online)	2040-3372
ISSN	2040-3364
DOI	10.1039/d3nr05119f
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Article ; Online: A sirtuin's role in preventing senescence by protecting ribosomal DNA.

Etchegaray, Jean-Pierre / Mostoslavsky, Raul

The Journal of biological chemistry

2018 Volume 293, Issue 28, Page(s) 11251–11252

Abstract: Ribosomes are encoded by many copies of ribosomal DNA (rDNA) packed into the nucleolus. High rates of transcription combined with highly repetitive sequences render rDNA loci particularly vulnerable to genomic instability, a proposed underlying cause of ... ...

Abstract	Ribosomes are encoded by many copies of ribosomal DNA (rDNA) packed into the nucleolus. High rates of transcription combined with highly repetitive sequences render rDNA loci particularly vulnerable to genomic instability, a proposed underlying cause of cellular senescence. The molecular mechanisms that maintain rDNA stability have remained unclear. A new paper elucidates a sirtuin-dependent mechanism that protects rDNA loci from genomic instability and prevents cellular senescence via heterochromatin silencing mediated by the chromatin remodeler SNF2H. This finding extends our understanding of chromatin dynamics within rDNA regions and offers new mechanistic insights into aging-related pathologies associated with genomic instability.
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Aging/pathology ; Cellular Senescence ; DNA, Ribosomal/genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Genomic Instability ; Humans ; Sirtuins/genetics ; Sirtuins/metabolism ; Transcription, Genetic
Chemical Substances	DNA, Ribosomal ; SIRT7 protein, human ; Sirtuins (EC 3.5.1.-)
Language	English
Publishing date	2018-07-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.H118.004040
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Article ; Online: TET3-mediated DNA oxidation is essential for intestinal epithelial cell response to stressors.

Gonzalez, Edward A / Liu, Yue / Wang, Dahui / Jeziorek, Maciej / Bandyopadhyay, Sheila / Rao, Anjana / Gao, Nan / Etchegaray, Jean-Pierre

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 37, Page(s) e2221405120

Abstract: DNA methylation functions as a repressive epigenetic mark that can be reversed by the Ten-eleven translocation (TET) family of DNA dioxygenases that sequentially oxidize 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- ... ...

Abstract	DNA methylation functions as a repressive epigenetic mark that can be reversed by the Ten-eleven translocation (TET) family of DNA dioxygenases that sequentially oxidize 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised by DNA base-excision repair factors leading to unmodified cytosines. TET enzymes were recently implicated as potential risk factors for inflammatory bowel disease (IBD), but the contribution of TET-mediated DNA oxidation to intestinal homeostasis and response to environmental stressors are unknown. Here, we show prominent roles of TET3 in regulating mouse intestinal epithelial differentiation and response to luminal stressors. Compared with wild-type littermates, mice with intestinal epithelial cell-specific ablation of
MeSH term(s)	Animals ; Humans ; Mice ; Colitis ; Dioxygenases ; DNA ; Enterocytes ; Oxidation-Reduction ; Paneth Cells
Chemical Substances	Dioxygenases (EC 1.13.11.-) ; DNA (9007-49-2) ; TET3 protein, human (EC 1.-) ; Tet3 protein, mouse (EC 1.13.11.-)
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2221405120
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Article ; Online: Low dose acetyl salicylic acid (LDA) mediates epigenetic changes in preeclampsia placental mesenchymal stem cells similar to cells from healthy pregnancy.

Krishnamoorthy, Kaila / Sherman, Lauren S / Romagano, Matthew P / El Far, Markos / Etchegaray, Jean-Pierre / Williams, Shauna F / Rameshwar, Pranela

Placenta

2023 Volume 137, Page(s) 49–58

Abstract: Introduction: Preeclampsia (PE) affects 2-8% of all pregnancies, and is the leading cause of maternal and fetal morbidity and mortality. We reported on pathophysiological changes in placenta mesenchymal stem cells (P-MSCs) in PE. P-MSCs can be isolated ... ...

Abstract	Introduction: Preeclampsia (PE) affects 2-8% of all pregnancies, and is the leading cause of maternal and fetal morbidity and mortality. We reported on pathophysiological changes in placenta mesenchymal stem cells (P-MSCs) in PE. P-MSCs can be isolated from different layers of the placenta at the interface between the fetus and mother. The ability of MSCs from other sources to be immune licensed as immune suppressor cells indicated that P-MSCs could mitigate fetal rejection. Acetylsalicylic acid (aspirin) is indicated for treating PE. Indeed, low-dose aspirin is recommended to prevent PE in high risk patients. Methods: We conducted robust computational analyses to study changes in gene expression in P-MSCs from PE and healthy term pregnancies as compared with PE-MSCs treated with low dose acetyl salicylic acid (LDA). Confocal microscopy studied phospho-H2AX levels in P-MSCs. Results: We identified changes in >400 genes with LDA, similar to levels of healthy pregnancy. The top canonical pathways that incorporate these genes were linked to DNA repair damage - Basic excision repair (BER), Nucleotide excision repair (NER) and DNA replication. A role for the sumoylation (SUMO) pathway, which could regulate gene expression and protein stabilization was significant although reduced as compared to BER and NER pathways. Labeling for phopho-H2AX indicated no evidence of double strand break in PE P-MSCs. Discussion: The overlapping of key genes within each pathway suggested a major role for LDA in the epigenetic landscape of PE P-MSCs. Overall, this study showed a new insight into how LDA reset the P-MSCs in PE subjects around the DNA.
MeSH term(s)	Humans ; Female ; Pregnancy ; Aspirin/pharmacology ; Aspirin/therapeutic use ; Pre-Eclampsia/metabolism ; Placenta/metabolism ; Epigenesis, Genetic ; Mesenchymal Stem Cells/metabolism ; Salicylic Acid/metabolism
Chemical Substances	Aspirin (R16CO5Y76E) ; Salicylic Acid (O414PZ4LPZ)
Language	English
Publishing date	2023-04-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2023.04.010
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Zs.A 1578: Show issues

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Article: Non-Coding RNAs as Mediators of Epigenetic Changes in Malignancies.

Kumar, Subhasree / Gonzalez, Edward A / Rameshwar, Pranela / Etchegaray, Jean-Pierre

Cancers

2020 Volume 12, Issue 12

Abstract: Non-coding RNAs (ncRNAs) are untranslated RNA molecules that regulate gene expressions. NcRNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (cRNAs) and piwi-interacting ... ...

Abstract	Non-coding RNAs (ncRNAs) are untranslated RNA molecules that regulate gene expressions. NcRNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (cRNAs) and piwi-interacting RNAs (piRNAs). This review focuses on two types of ncRNAs: microRNAs (miRNAs) or short interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs). We highlight the mechanisms by which miRNAs and lncRNAs impact the epigenome in the context of cancer. Both miRNAs and lncRNAs have the ability to interact with numerous epigenetic modifiers and transcription factors to influence gene expression. The aberrant expression of these ncRNAs is associated with the development and progression of tumors. The primary reason for their deregulated expression can be attributed to epigenetic alterations. Epigenetic alterations can cause the misregulation of ncRNAs. The experimental evidence indicated that most abnormally expressed ncRNAs impact cellular proliferation and apoptotic pathways, and such changes are cancer-dependent. In vitro and in vivo experiments show that, depending on the cancer type, either the upregulation or downregulation of ncRNAs can prevent the proliferation and progression of cancer. Therefore, a better understanding on how ncRNAs impact tumorigenesis could serve to develop new therapeutic treatments. Here, we review the involvement of ncRNAs in cancer epigenetics and highlight their use in clinical therapy.
Language	English
Publishing date	2020-12-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12123657
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Article ; Online: Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes.

Etchegaray, Jean-Pierre / Mostoslavsky, Raul

Molecular cell

2016 Volume 62, Issue 5, Page(s) 695–711

Abstract: The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in tune with nutritional conditions. The regulation of cell-specific transcriptional networks is ... ...

Abstract	The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in tune with nutritional conditions. The regulation of cell-specific transcriptional networks is accomplished by an epigenetic program via chromatin-modifying enzymes, whose activity is directly dependent on metabolites such as acetyl-coenzyme A, S-adenosylmethionine, and NAD+, among others. Therefore, these nuclear activities are directly influenced by the nutritional status of the cell. In addition to nutritional availability, this highly collaborative program between epigenetic dynamics and metabolism is further interconnected with other environmental cues provided by the day-night cycles imposed by circadian rhythms. Herein, we review molecular pathways and their metabolites associated with epigenetic adaptations modulated by histone- and DNA-modifying enzymes and their responsiveness to the environment in the context of health and disease.
MeSH term(s)	Adaptation, Physiological ; Animals ; Cell Nucleus/metabolism ; Cellular Microenvironment ; Chromatin Assembly and Disassembly ; Circadian Rhythm ; DNA Methylation ; Energy Metabolism ; Epigenesis, Genetic ; Genetic Predisposition to Disease ; Histones/metabolism ; Humans ; Phenotype ; Transcription, Genetic
Chemical Substances	Histones
Language	English
Publishing date	2016-06-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2016.05.029
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Zs.A 5055: Show issues

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Article: Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.

Sorrentino, Vincent G / Thota, Srijan / Gonzalez, Edward A / Rameshwar, Pranela / Chang, Victor T / Etchegaray, Jean-Pierre

Pharmaceuticals (Basel, Switzerland)

2021 Volume 14, Issue 7

Abstract: Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA ... ...

Abstract	Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA hypomethylating agents such as decitabine and azacitidine are used as therapeutic treatments and have shown to promote expression of genes involved in tumor suppression, apoptosis, and immune response. Another anti-cancer drug, the proteasome inhibitor bortezomib, is used as a chemotherapeutic treatment for multiple myeloma (MM). Phase III clinical trials of decitabine and azacitidine used alone and in combination with other chemotherapeutics demonstrated their capacity to treat hematological malignancies and prolong the survival of MDS and AML patients. Although phase III clinical trials examining bortezomib's role in MDS and AML patients are limited, its underlying mechanisms in MM highlight its potential as a chemotherapeutic for such malignancies. Further research is needed to better understand how the epigenetic mechanisms mediated by these chemotherapeutic agents and their targeted gene networks are associated with the development and progression of MDS into AML. This review discusses the mechanisms by which decitabine, azacitidine, and bortezomib alter epigenetic programs and their results from phase III clinical trials.
Language	English
Publishing date	2021-07-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph14070641
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Article: Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes

Etchegaray, Jean-Pierre / Raul Mostoslavsky

Molecular cell. 2016 June 02, v. 62, no. 5

2016

Abstract	The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in tune with nutritional conditions. The regulation of cell-specific transcriptional networks is accomplished by an epigenetic program via chromatin-modifying enzymes, whose activity is directly dependent on metabolites such as acetyl-coenzyme A, S-adenosylmethionine, and NAD+, among others. Therefore, these nuclear activities are directly influenced by the nutritional status of the cell. In addition to nutritional availability, this highly collaborative program between epigenetic dynamics and metabolism is further interconnected with other environmental cues provided by the day-night cycles imposed by circadian rhythms. Herein, we review molecular pathways and their metabolites associated with epigenetic adaptations modulated by histone- and DNA-modifying enzymes and their responsiveness to the environment in the context of health and disease.
Keywords	acetyl coenzyme A ; circadian rhythm ; enzymes ; epigenetics ; metabolism ; metabolites ; nutritional status ; S-adenosylmethionine ; transcription (genetics)
Language	English
Dates of publication	2016-0602
Size	p. 695-711.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2016.05.029
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Cell Fate by SIRT6 and TETs.

Etchegaray, Jean-Pierre / Mostoslavsky, Raul

Cell cycle (Georgetown, Tex.)

2015 Volume 14, Issue 14, Page(s) 2187–2188

MeSH term(s)	5-Methylcytosine/analogs & derivatives ; Animals ; Cell Differentiation ; Cytosine/analogs & derivatives ; Cytosine/metabolism ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Humans ; Mixed Function Oxygenases ; Proto-Oncogene Proteins/metabolism ; Sirtuins/deficiency ; Sirtuins/genetics ; Sirtuins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Proto-Oncogene Proteins ; Transcription Factors ; 5-hydroxymethylcytosine (1123-95-1) ; 5-Methylcytosine (6R795CQT4H) ; Cytosine (8J337D1HZY) ; Mixed Function Oxygenases (EC 1.-) ; TET1 protein, human (EC 1.-) ; TET2 protein, human (EC 1.13.11.-) ; SIRT6 protein, human (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-)
Language	English
Publishing date	2015-06-11
Publishing country	United States
Document type	Editorial
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2015.1060768
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Zs.A 5881: Show issues

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Article ; Online: Epigenetic dynamics in cancer stem cell dormancy.

Ferrer, Alejandra I / Trinidad, Jonathan R / Sandiford, Oleta / Etchegaray, Jean-Pierre / Rameshwar, Pranela

Cancer metastasis reviews

2020 Volume 39, Issue 3, Page(s) 721–738

Abstract: Cancer remains one of the most challenging diseases despite significant advances of early diagnosis and therapeutic treatments. Cancerous tumors are composed of various cell types including cancer stem cells capable of self-renewal, proliferation, ... ...

Abstract	Cancer remains one of the most challenging diseases despite significant advances of early diagnosis and therapeutic treatments. Cancerous tumors are composed of various cell types including cancer stem cells capable of self-renewal, proliferation, differentiation, and invasion of distal tumor sites. Most notably, these cells can enter a dormant cellular state that is resistant to conventional therapies. Thereby, cancer stem cells have the intrinsic potential for tumor initiation, tumor growth, metastasis, and tumor relapse after therapy. Both genetic and epigenetic alterations are attributed to the formation of multiple tumor types. This review is focused on how epigenetic dynamics involving DNA methylation and DNA oxidations are implicated in breast cancer and glioblastoma multiforme. The emergence and progression of these cancer types rely on cancer stem cells with the capacity to enter quiescence also known as a dormant cellular state, which dictates the distinct tumorigenic aggressiveness between breast cancer and glioblastomas.
MeSH term(s)	Animals ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; DNA Methylation ; DNA, Neoplasm/genetics ; DNA, Neoplasm/metabolism ; Epigenesis, Genetic ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Oxidation-Reduction
Chemical Substances	DNA, Neoplasm
Language	English
Publishing date	2020-05-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-020-09882-x
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