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Article ; Online: Depletion of

Neelamraju, Yaseswini / Gjini, Evisa / Chhangawala, Sagar / Fan, Hao / He, Shuning / Jing, Chang-Bin / Nguyen, Ashley T / Prajapati, Subhash / Sheridan, Caroline / Houvras, Yariv / Melnick, Ari / Look, A Thomas / Garrett-Bakelman, Francine E

Frontiers in hematology

2023 Volume 2

Abstract: Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (: Methods: In the current ... ...

Abstract	Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 ( Methods: In the current study, we collected progenitor cells from the kidney marrows of the adult Results and discussion: A global increase in DNA methylation of gene promoter regions and CpG islands was observed in
Language	English
Publishing date	2023-09-14
Publishing country	Switzerland
Document type	Journal Article
ISSN	2813-3935
ISSN (online)	2813-3935
DOI	10.3389/frhem.2023.1235170
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Article ; Online: Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks.

Nishtala, Sneha / Neelamraju, Yaseswini / Janga, Sarath Chandra

Scientific reports

2016 Volume 6, Page(s) 25711

Abstract: RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 ...

Abstract	RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.
MeSH term(s)	Binding Sites/genetics ; Eukaryotic Cells/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genome, Fungal/genetics ; Humans ; Models, Genetic ; Oligonucleotide Array Sequence Analysis/methods ; Protein Binding ; RNA/genetics ; RNA/metabolism ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA-Binding Motifs/genetics ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	RNA, Fungal ; RNA-Binding Proteins ; Saccharomyces cerevisiae Proteins ; RNA (63231-63-0)
Language	English
Publishing date	2016-05-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep25711
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Article ; Online: Database of RNA binding protein expression and disease dynamics (READ DB).

Hashemikhabir, Seyedsasan / Neelamraju, Yaseswini / Janga, Sarath Chandra

Database : the journal of biological databases and curation

2015 Volume 2015, Page(s) bav072

Abstract: RNA Binding Protein (RBP) Expression and Disease Dynamics database (READ DB) is a non-redundant, curated database of human RBPs. RBPs curated from different experimental studies are reported with their annotation, tissue-wide RNA and protein expression ... ...

Abstract	RNA Binding Protein (RBP) Expression and Disease Dynamics database (READ DB) is a non-redundant, curated database of human RBPs. RBPs curated from different experimental studies are reported with their annotation, tissue-wide RNA and protein expression levels, evolutionary conservation, disease associations, protein-protein interactions, microRNA predictions, their known RNA recognition sequence motifs as well as predicted binding targets and associated functional themes, providing a one stop portal for understanding the expression, evolutionary trajectories and disease dynamics of RBPs in the context of post-transcriptional regulatory networks.
MeSH term(s)	Animals ; Databases, Genetic ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA-Binding Proteins/biosynthesis ; RNA-Binding Proteins/genetics
Chemical Substances	MicroRNAs ; RNA-Binding Proteins
Language	English
Publishing date	2015-07-25
Publishing country	England
Document type	Dataset ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/bav072
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Article ; Online: The human RBPome: from genes and proteins to human disease.

Neelamraju, Yaseswini / Hashemikhabir, Seyedsasan / Janga, Sarath Chandra

Journal of proteomics

2015 Volume 127, Issue Pt A, Page(s) 61–70

Abstract: RNA binding proteins (RBPs) play a central role in mediating post transcriptional regulation of genes. However less is understood about them and their regulatory mechanisms. In this study, we construct a catalogue of 1344 experimentally confirmed RBPs. ... ...

Abstract	RNA binding proteins (RBPs) play a central role in mediating post transcriptional regulation of genes. However less is understood about them and their regulatory mechanisms. In this study, we construct a catalogue of 1344 experimentally confirmed RBPs. The domain architecture of RBPs enabled us to classify them into three groups - Classical (29%), Non-classical (19%) and unclassified (52%). A higher percentage of proteins with unclassified domains reveals the presence of various uncharacterised motifs that can potentially bind RNA. RBPs were found to be highly disordered compared to Non-RBPs (p<2.2e-16, Fisher's exact test), suggestive of a dynamic regulatory role of RBPs in cellular signalling and homeostasis. Evolutionary analysis in 62 different species showed that RBPs are highly conserved compared to Non-RBPs (p<2.2e-16, Wilcox-test), reflecting the conservation of various biological processes like mRNA splicing and ribosome biogenesis. The expression patterns of RBPs from human proteome map revealed that ~40% of them are ubiquitously expressed and ~60% are tissue-specific. RBPs were also seen to be highly associated with several neurological disorders, cancer and inflammatory diseases. Anatomical contexts like B cells, T-cells, foetal liver and foetal brain were found to be strongly enriched for RBPs, implying a prominent role of RBPs in immune responses and different developmental stages. The catalogue and meta-analysis presented here should form a foundation for furthering our understanding of RBPs and the cellular networks they control, in years to come. This article is part of a Special Issue entitled: Proteomics in India.
MeSH term(s)	Humans ; Inflammation/genetics ; Inflammation/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Nervous System Diseases/genetics ; Nervous System Diseases/metabolism ; Proteome/classification ; Proteome/genetics ; Proteome/metabolism ; RNA-Binding Proteins/classification ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
Chemical Substances	Neoplasm Proteins ; Proteome ; RNA-Binding Proteins
Language	English
Publishing date	2015-09-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2015.04.031
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Article: Mutational landscape of RNA-binding proteins in human cancers

Neelamraju, Yaseswini / Gonzalez-Perez, Abel / Bhat-Nakshatri, Poornima / Nakshatri, Harikrishna / Janga, Sarath Chandra

RNA biology. 2018 Jan. 2, v. 15, no. 1

2018

Abstract: RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the ... ...

Abstract	RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations. Functional analysis of these RBPs revealed the enrichment of pathways associated with apoptosis, splicing and translation. Using the OncodriveFM framework, we also identified more than 200 candidate driver RBPs that were found to accumulate functionally impactful mutations in at least one cancer. Expression levels of 15% of these driver RBPs exhibited significant difference, when transcriptome groups with and without deleterious mutations were compared. Functional interaction network of the driver RBPs revealed the enrichment of spliceosomal machinery, suggesting a plausible mechanism for tumorogenesis while network analysis of the protein interactions between RBPs unambiguously revealed the higher degree, betweenness and closeness centrality for driver RBPs compared to non-drivers. Analysis to reveal cancer-specific Ribonucleoprotein (RNP) mutational hotspots showed extensive rewiring even among common drivers between cancer types. Knockdown experiments on pan-cancer drivers such as SF3B1 and PRPF8 in breast cancer cell lines, revealed cancer subtype specific functions like selective stem cell features, indicating a plausible means for RBPs to mediate cancer-specific phenotypes. Hence, this study would form a foundation to uncover the contribution of the mutational spectrum of RBPs in dysregulating the post-transcriptional regulatory networks in different cancer types.
Keywords	RNA ; apoptosis ; breast neoplasms ; genome ; humans ; mutation ; neoplasm cells ; ribonucleoproteins ; spliceosomes ; stem cells ; transcriptome
Language	English
Dates of publication	2018-0102
Size	p. 115-129.
Publishing place	Taylor & Francis
Document type	Article
ISSN	1555-8584
DOI	10.1080/15476286.2017.1391436
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Article: The human RBPome: From genes and proteins to human disease

Neelamraju, Yaseswini / Sarath Chandra Janga / Seyedsasan Hashemikhabir

Journal of proteomics. 2015 Sept. 08, v. 127

2015

Abstract	RNA binding proteins (RBPs) play a central role in mediating post transcriptional regulation of genes. However less is understood about them and their regulatory mechanisms. In this study, we construct a catalogue of 1344 experimentally confirmed RBPs. The domain architecture of RBPs enabled us to classify them into three groups — Classical (29%), Non-classical (19%) and unclassified (52%). A higher percentage of proteins with unclassified domains reveals the presence of various uncharacterised motifs that can potentially bind RNA. RBPs were found to be highly disordered compared to Non-RBPs (p<2.2e-16, Fisher's exact test), suggestive of a dynamic regulatory role of RBPs in cellular signalling and homeostasis. Evolutionary analysis in 62 different species showed that RBPs are highly conserved compared to Non-RBPs (p<2.2e-16, Wilcox-test), reflecting the conservation of various biological processes like mRNA splicing and ribosome biogenesis. The expression patterns of RBPs from human proteome map revealed that ~40% of them are ubiquitously expressed and ~60% are tissue-specific. RBPs were also seen to be highly associated with several neurological disorders, cancer and inflammatory diseases. Anatomical contexts like B cells, T-cells, foetal liver and foetal brain were found to be strongly enriched for RBPs, implying a prominent role of RBPs in immune responses and different developmental stages. The catalogue and meta-analysis presented here should form a foundation for furthering our understanding of RBPs and the cellular networks they control, in years to come.This article is part of a Special Issue entitled: Proteomics in India.
Keywords	biogenesis ; brain ; cell communication ; developmental stages ; genes ; homeostasis ; human diseases ; humans ; immune response ; liver ; messenger RNA ; meta-analysis ; neoplasms ; nervous system diseases ; proteome ; proteomics ; ribosomes ; RNA-binding proteins ; T-lymphocytes ; transcription (genetics)
Language	English
Dates of publication	2015-0908
Size	p. 61-70.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2015.04.031
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Article ; Online: Mutational landscape of RNA-binding proteins in human cancers.

Neelamraju, Yaseswini / Gonzalez-Perez, Abel / Bhat-Nakshatri, Poornima / Nakshatri, Harikrishna / Janga, Sarath Chandra

RNA biology

2017 Volume 15, Issue 1, Page(s) 115–129

Abstract	RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations. Functional analysis of these RBPs revealed the enrichment of pathways associated with apoptosis, splicing and translation. Using the OncodriveFM framework, we also identified more than 200 candidate driver RBPs that were found to accumulate functionally impactful mutations in at least one cancer. Expression levels of 15% of these driver RBPs exhibited significant difference, when transcriptome groups with and without deleterious mutations were compared. Functional interaction network of the driver RBPs revealed the enrichment of spliceosomal machinery, suggesting a plausible mechanism for tumorogenesis while network analysis of the protein interactions between RBPs unambiguously revealed the higher degree, betweenness and closeness centrality for driver RBPs compared to non-drivers. Analysis to reveal cancer-specific Ribonucleoprotein (RNP) mutational hotspots showed extensive rewiring even among common drivers between cancer types. Knockdown experiments on pan-cancer drivers such as SF3B1 and PRPF8 in breast cancer cell lines, revealed cancer subtype specific functions like selective stem cell features, indicating a plausible means for RBPs to mediate cancer-specific phenotypes. Hence, this study would form a foundation to uncover the contribution of the mutational spectrum of RBPs in dysregulating the post-transcriptional regulatory networks in different cancer types.
MeSH term(s)	Carcinogenesis/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Gene Knockdown Techniques ; Genome, Human/genetics ; Humans ; Mutation ; Neoplasms/genetics ; Neoplasms/pathology ; Phosphoproteins/genetics ; RNA Splicing/genetics ; RNA Splicing Factors/genetics ; RNA-Binding Proteins/genetics ; Spliceosomes/genetics ; Transcriptome/genetics
Chemical Substances	PRPF8 protein, human ; Phosphoproteins ; RNA Splicing Factors ; RNA-Binding Proteins ; SF3B1 protein, human
Language	English
Publishing date	2017-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1555-8584
ISSN (online)	1555-8584
DOI	10.1080/15476286.2017.1391436
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Article ; Online: Prognostic impact of HOTAIR expression is restricted to ER-negative breast cancers.

Gökmen-Polar, Yesim / Vladislav, I Tudor / Neelamraju, Yaseswini / Janga, Sarath C / Badve, Sunil

Scientific reports

2015 Volume 5, Page(s) 8765

Abstract: Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine ... ...

Abstract	Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity or with other study parameters (age, tumor size and grade, expression status). Further analysis of TCGA dataset showed that HOTAIR expression was lower in ductal carcinomas but higher in ER-negative tumors. Overexpression of HOTAIR was not associated with nodal metastases or prognosis in ER-positive patients. Its function as a poor prognostic indicator in ER-negative patients was restricted to node-positive patients. HOTAIR appears to be a marker for lymphatic metastases rather than hematogenous metastases in ER-negative patients.
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Cohort Studies ; Datasets as Topic ; Female ; Gene Expression ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Neoplasm Grading ; Prognosis ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Estrogen/metabolism ; Tumor Burden
Chemical Substances	Biomarkers, Tumor ; HOTAIR long untranslated RNA, human ; RNA, Long Noncoding ; Receptors, Estrogen ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2015-03-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep08765
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Article ; Online: Uncovering RNA binding proteins associated with age and gender during liver maturation.

Chaturvedi, Praneet / Neelamraju, Yaseswini / Arif, Waqar / Kalsotra, Auinash / Janga, Sarath Chandra

Scientific reports

2015 Volume 5, Page(s) 9512

Abstract: In the present study, we perform an association analysis focusing on the expression changes of 1344 RNA Binding proteins (RBPs) as a function of age and gender in human liver. We identify 88 and 45 RBPs to be significantly associated with age and gender ... ...

Abstract	In the present study, we perform an association analysis focusing on the expression changes of 1344 RNA Binding proteins (RBPs) as a function of age and gender in human liver. We identify 88 and 45 RBPs to be significantly associated with age and gender respectively. Experimental verification of several of the predicted associations in mice confirmed our findings. Our results suggest that a small fraction of the gender-associated RBPs (~40%) are expressed higher in males than females. Altogether, these observations show that several of these RBPs are important and conserved regulators in maintaining liver function. Further analysis of the protein interaction network of RBPs associated with age and gender based on the centrality measures like degree, betweenness and closeness revealed that several of these RBPs might be prominent players in aging liver and impart gender specific alterations in gene expression via the formation of protein complexes. Indeed, both age and gender-associated RBPs in liver were found to show significantly higher clustering coefficients and network centrality measures compared to non-associated RBPs. The compendium of RBPs and this study will help us gain insight into the role of post-transcriptional regulatory molecules in aging and gender specific expression of genes.
MeSH term(s)	Age Factors ; Animals ; Cluster Analysis ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Liver/growth & development ; Liver/metabolism ; Male ; Mice ; Protein Interaction Mapping ; Protein Interaction Maps ; RNA-Binding Proteins/genetics ; Rats ; Reproducibility of Results ; Sex Factors ; Transcriptome
Chemical Substances	RNA-Binding Proteins
Language	English
Publishing date	2015-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep09512
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Article ; Online: Correction: Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.

Rapaport, Franck / Seier, Kenneth / Neelamraju, Yaseswini / Hassane, Duane / Baslan, Timour / Gildea, Daniel T / Haddox, Samuel / Lee, Tak / Murdock, H Moses / Sheridan, Caroline / Thurmond, Alexis / Wang, Ling / Carroll, Martin / Cripe, Larry D / Fernandez, Hugo / Mason, Christopher E / Paietta, Elisabeth / Roboz, Gail J / Sun, Zhuoxin /

Tallman, Martin S / Zhang, Yanming / Gönen, Mithat / Levine, Ross / Melnick, Ari M / Kleppe, Maria / Garrett-Bakelman, Francine E

Blood cancer journal

2023 Volume 13, Issue 1, Page(s) 103

Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-023-00862-2
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