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Article: TTBK2

Muñoz-Estrada, Jesús / Nguyen, Abraham V / Goetz, Sarah C

bioRxiv : the preprint server for biology

2023

Abstract: Frameshift mutations ... ...

Abstract	Frameshift mutations in
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.31.526333
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Article: Biomarkers in Alzheimer's Disease: Are Olfactory Neuronal Precursors Useful for

Santillán-Morales, Valeria / Rodriguez-Espinosa, Norberto / Muñoz-Estrada, Jesús / Alarcón-Elizalde, Salvador / Acebes, Ángel / Benítez-King, Gloria

Brain sciences

2024 Volume 14, Issue 1

Abstract: Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is ... ...

Abstract	Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. AD is a multifactorial disease, and knowing its underlying pathological mechanisms is crucial to propose new and valuable biomarkers. In this review, we summarize some of the main biomarkers described in AD, which have been evaluated mainly by imaging studies in cerebrospinal fluid and blood samples. Furthermore, we describe and propose neuronal precursors derived from the olfactory neuroepithelium as a potential resource to evaluate some of the widely known biomarkers of AD and to gear toward searching for new biomarkers. These neuronal lineage cells, which can be obtained directly from patients through a non-invasive and outpatient procedure, display several characteristics that validate them as a surrogate model to study the central nervous system, allowing the analysis of AD pathophysiological processes. Moreover, the ease of obtaining and harvesting endows them as an accessible and powerful resource to evaluate biomarkers in clinical practice.
Language	English
Publishing date	2024-01-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci14010046
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Article ; Online: The Transition Zone Protein AHI1 Regulates Neuronal Ciliary Trafficking of MCHR1 and Its Downstream Signaling Pathway.

Hsiao, Yi-Chun / Muñoz-Estrada, Jesús / Tuz, Karina / Ferland, Russell J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2021 Volume 41, Issue 17, Page(s) 3932–3943

Abstract: The Abelson-helper integration site 1 ( ...

Abstract	The Abelson-helper integration site 1 (
MeSH term(s)	Abnormalities, Multiple/genetics ; Abnormalities, Multiple/physiopathology ; Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/physiology ; Animals ; Cell Membrane/physiology ; Cerebellum/abnormalities ; Cerebellum/physiopathology ; Cilia/physiology ; Cyclic AMP/metabolism ; Eye Abnormalities/genetics ; Eye Abnormalities/physiopathology ; Female ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/physiopathology ; MAP Kinase Signaling System/genetics ; MAP Kinase Signaling System/physiology ; Mice ; Mice, Knockout ; Neurons/physiology ; Pregnancy ; Receptors, Somatostatin/genetics ; Receptors, Somatostatin/physiology ; Retina/abnormalities ; Retina/physiopathology ; Signal Transduction/genetics ; Signal Transduction/physiology
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Ahi1 protein, mouse ; Mchr1 protein, mouse ; Receptors, Somatostatin ; Cyclic AMP (E0399OZS9N)
Language	English
Publishing date	2021-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2993-20.2021
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Article ; Online: Ahi1 promotes Arl13b ciliary recruitment, regulates Arl13b stability and is required for normal cell migration.

Muñoz-Estrada, Jesús / Ferland, Russell J

Journal of cell science

2019 Volume 132, Issue 17

Abstract: Mutations in the Abelson-helper integration site 1 ( ...

Abstract	Mutations in the Abelson-helper integration site 1 (
MeSH term(s)	ADP-Ribosylation Factors/genetics ; ADP-Ribosylation Factors/metabolism ; Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Cell Movement/physiology ; Cilia/metabolism ; Fibroblasts/metabolism ; Mice ; Mice, Knockout ; Mutation ; Protein Transport ; Signal Transduction
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Ahi1 protein, mouse ; Arl13b protein, mouse ; ADP-Ribosylation Factors (EC 3.6.5.2)
Language	English
Publishing date	2019-09-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.230680
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Article ; Online: Altered subcellular distribution of the 75-kDa DISC1 isoform, cAMP accumulation, and decreased neuronal migration in schizophrenia and bipolar disorder: implications for neurodevelopment.

Muñoz-Estrada, Jesús / Benítez-King, Gloria / Berlanga, Carlos / Meza, Isaura

CNS neuroscience & therapeutics

2015 Volume 21, Issue 5, Page(s) 446–453

Abstract: Background: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates microtubule stability, migration, and cAMP signaling in mammalian cell lines and mouse brain tissue. ... ...

Abstract	Background: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates microtubule stability, migration, and cAMP signaling in mammalian cell lines and mouse brain tissue. cAMP is a regulator of microtubule organization and migration in neurons. Aberrant microtubule organization has been observed in olfactory neuronal precursors (ONP) derived from patients with SZ and BD, which suggests involvement of DISC1 and cAMP. However, the biology of DISC1 in the physiopathology of psychiatric conditions remains elusive. Aims: Herein, utilizing ONP obtained from SZ, BD patients and healthy subjects, we have studied DISC1 expression, protein levels, and subcellular distribution by qRT-PCR, immunoblotting, subcellular fractionation, and confocal microscopy. Cell migration and cAMP accumulation were assessed by Transwell and PKA competition assays. Results: We found increased levels of the 75-kDa DISC1 isoform in total cell extracts of ONP from patients with SZ and BD compared with controls. Subcellular distribution showed a significant decrease of cytoplasmic DISC1 concomitant with its augmented levels in transcription sites. Moreover, significant cAMP accumulation and diminished migration were also observed in patients' cells. Conclusion: Alterations of DISC1 levels and its cellular distribution, which negatively modify cAMP homeostasis, microtubule organization, and cell migration, in ONP from patients with SZ and BD, suggest that their presence in early stages of brain development may impact brain maturation and function.
MeSH term(s)	Bipolar Disorder/pathology ; Bipolar Disorder/physiopathology ; Cell Movement/physiology ; Cells, Cultured ; Cyclic AMP/metabolism ; Humans ; Isomerism ; Microtubules/metabolism ; Microtubules/pathology ; Nasal Mucosa/pathology ; Nasal Mucosa/physiopathology ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/pathology ; Neural Stem Cells/physiology ; Neurons/pathology ; Neurons/physiology ; RNA, Messenger/metabolism ; Schizophrenia/pathology ; Schizophrenia/physiopathology ; Subcellular Fractions/metabolism
Chemical Substances	DISC1 protein, human ; Nerve Tissue Proteins ; RNA, Messenger ; Cyclic AMP (E0399OZS9N)
Language	English
Publishing date	2015-01-24
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2423467-9
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.12377
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Article ; Online: Primary cilia formation is diminished in schizophrenia and bipolar disorder: A possible marker for these psychiatric diseases.

Muñoz-Estrada, Jesús / Lora-Castellanos, Alejandra / Meza, Isaura / Alarcón Elizalde, Salvador / Benítez-King, Gloria

Schizophrenia research

2017 Volume 195, Page(s) 412–420

Abstract: Primary cilium (PC) is a microtubule-rich organelle that protrudes from the plasma membrane and acts as a cellular antenna sensing extracellular signals during brain development. DISC1 (Disrupted-in-Schizophrenia-1) is involved in PC formation and is ... ...

Abstract	Primary cilium (PC) is a microtubule-rich organelle that protrudes from the plasma membrane and acts as a cellular antenna sensing extracellular signals during brain development. DISC1 (Disrupted-in-Schizophrenia-1) is involved in PC formation and is considered a risk factor for neuropsychiatric disorders. We have previously described altered subcellular distribution of DISC1 and an aberrant microtubule organization in olfactory neuronal precursors (ONP) obtained from schizophrenia (SCZ) and bipolar disorder (BD) patients. Herein, we analyzed in vitro PC formation in healthy control subjects, SCZ and BD patients. The results indicated that 66.73±4.33% of ONP from control subjects showed immunostaining for the PC marker, acetylated α-tubulin. By contrast, only a small percentage of cells in culture from paranoid SCZ and BD patients showed PC staining (SCZ, 12.8±4.43%; BD, 12.32±5.86%). However, cells from an affected proband with disorganized SCZ and a subject with BD displayed a higher percentage of cells with cilia (SCZ, 42.20%; BD, 38.59%). Additionally, cilia elongation was observed in lithium-treated ONP derived from all groups, with a more evident response in cells from the BD group. The present study provides novel evidence that the molecular pathways involved in PC formation are defective in SCZ and BD, and impairment in these processes may be involved in the physiopathology of both diseases. Our observations also suggest that ONP is a patient-derived cell model with a potential use for diagnosis and high-throughput drug screening for brain diseases.
MeSH term(s)	Adenylyl Cyclases/metabolism ; Adult ; Bipolar Disorder/pathology ; Cilia/pathology ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Male ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Neurons/drug effects ; Neurons/pathology ; Schizophrenia/pathology ; Time Factors ; Tubulin/metabolism ; Valproic Acid/pharmacology ; Young Adult
Chemical Substances	Enzyme Inhibitors ; Tubulin ; Valproic Acid (614OI1Z5WI) ; Adenylyl Cyclases (EC 4.6.1.1) ; adenylate cyclase 3 (EC 4.6.1.1)
Language	English
Publishing date	2017-09-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2017.08.055
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Article ; Online: Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice.

Estrada-Reyes, Rosa / Quero-Chávez, Daniel B / Trueta, Citlali / Miranda, Armida / Valdés-Tovar, Marcela / Alarcón-Elizalde, Salvador / Oikawa-Sala, Julián / Argueta, Jesús / Constantino-Jonapa, Luis A / Muñoz-Estrada, Jesús / Dubocovich, Margarita L / Benítez-King, Gloria

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract: Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, ... ...

Abstract	Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.
MeSH term(s)	Animals ; Antidepressive Agents/administration & dosage ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Depression/drug therapy ; Drug Combinations ; Drug Synergism ; Ketamine/administration & dosage ; Ketamine/pharmacology ; Ketamine/therapeutic use ; Male ; Melatonin/administration & dosage ; Melatonin/pharmacology ; Melatonin/therapeutic use ; Mice ; Neurogenesis/drug effects
Chemical Substances	Antidepressive Agents ; Drug Combinations ; Ketamine (690G0D6V8H) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179225
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Article ; Online: BranchAnalysis2D/3D automates morphometry analyses of branching structures.

Srinivasan, Aditya / Muñoz-Estrada, Jesús / Bourgeois, Justin R / Nalwalk, Julia W / Pumiglia, Kevin M / Sheen, Volney L / Ferland, Russell J

Journal of neuroscience methods

2017 Volume 294, Page(s) 1–6

Abstract: Background: Morphometric analyses of biological features have become increasingly common in recent years with such analyses being subject to a large degree of observer bias, variability, and time consumption. While commercial software packages exist to ... ...

Abstract	Background: Morphometric analyses of biological features have become increasingly common in recent years with such analyses being subject to a large degree of observer bias, variability, and time consumption. While commercial software packages exist to perform these analyses, they are expensive, require extensive user training, and are usually dependent on the observer tracing the morphology. New method: To address these issues, we have developed a broadly applicable, no-cost ImageJ plugin we call 'BranchAnalysis2D/3D', to perform morphometric analyses of structures with branching morphologies, such as neuronal dendritic spines, vascular morphology, and primary cilia. Results: Our BranchAnalysis2D/3D algorithm allows for rapid quantification of the length and thickness of branching morphologies, independent of user tracing, in both 2D and 3D data sets. Comparison with existing methods: We validated the performance of BranchAnalysis2D/3D against pre-existing software packages using trained human observers and images from brain and retina. We found that the BranchAnalysis2D/3D algorithm outputs results similar to available software (i.e., Metamorph, AngioTool, Neurolucida), while allowing faster analysis times and unbiased quantification. Conclusions: BranchAnalysis2D/3D allows inexperienced observers to output results like a trained observer but more efficiently, thereby increasing the consistency, speed, and reliability of morphometric analyses.
MeSH term(s)	Algorithms ; Animals ; Brain/cytology ; Imaging, Three-Dimensional/methods ; Mice ; Microscopy, Confocal/methods ; Neurons/cytology ; Observer Variation ; Reproducibility of Results ; Retina/anatomy & histology ; Software
Language	English
Publishing date	2017-10-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2017.10.017
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Article: Ouabain modulates ciliogenesis in epithelial cells

Larre, Isabel / Castillo, Aida / Flores-Maldonado, Catalina / Contreras, Ruben G / Galvan, Ivan / Muñoz-Estrada, Jesus / Cereijido, Marcelino

Proceedings of the National Academy of Sciences of the United States of America. 2011 Dec. 20, v. 108, no. 51

2011

Abstract: The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances ... ...

Abstract	The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances vectorially. In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well. We gauge polarity through the development of a cilium at the apical domain of Madin-Darby canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for the Na+ and H2O permeability of the TJs, is also present at the cilium, as it colocalizes and coprecipitates with acetylated α-tubulin. Ouabain modulates claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and ouabain-resistant MDCK cells, we show that ouabain acts through Na+,K+-ATPase. Taken together, our previous and present results support the possibility that ouabain constitutes a hormone that modulates the transporting epithelial phenotype, thereby playing a crucial role in metazoan life.
Keywords	dogs ; epithelial cells ; extracellular space ; kidney cells ; kidneys ; ouabain ; permeability ; phenotype ; sodium-potassium-exchanging ATPase ; tight junctions ; tubulin ; water
Language	English
Dates of publication	2011-1220
Size	p. 20591-20596.
Publishing place	National Academy of Sciences
Document type	Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ouabain modulates ciliogenesis in epithelial cells.

Larre, Isabel / Castillo, Aida / Flores-Maldonado, Catalina / Contreras, Ruben G / Galvan, Ivan / Muñoz-Estrada, Jesus / Cereijido, Marcelino

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

2011 Volume 108, Issue 51, Page(s) 20591–20596

Abstract	The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances vectorially. In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well. We gauge polarity through the development of a cilium at the apical domain of Madin-Darby canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for the Na(+) and H(2)O permeability of the TJs, is also present at the cilium, as it colocalizes and coprecipitates with acetylated α-tubulin. Ouabain modulates claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and ouabain-resistant MDCK cells, we show that ouabain acts through Na(+),K(+)-ATPase. Taken together, our previous and present results support the possibility that ouabain constitutes a hormone that modulates the transporting epithelial phenotype, thereby playing a crucial role in metazoan life.
MeSH term(s)	Animals ; Cadherins/metabolism ; Cell Adhesion ; Cell Communication ; Cell Line ; Cell Proliferation ; Cilia/metabolism ; Claudins/metabolism ; Dogs ; Epithelial Cells/metabolism ; Immunoprecipitation ; Magnetic Resonance Spectroscopy/methods ; Ouabain/chemistry ; Ouabain/pharmacology ; Sodium-Potassium-Exchanging ATPase/metabolism ; Steroids/metabolism ; Tight Junctions ; Time Factors
Chemical Substances	Cadherins ; Claudins ; Steroids ; Ouabain (5ACL011P69) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
Language	English
Publishing date	2011-12-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1102617108
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