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Article ; Online: Allelic combinations of Hd1, Hd16, and Ghd7 exhibit pleiotropic effects on agronomic traits in rice.

Lee, Seung Young / Jeung, Ji-Ung / Mo, Youngjun

2024 Volume 14, Issue 3

Abstract: Heading date is a critical agronomic trait that significantly affects grain yield and quality in rice. As early heading is typically associated with reduced yield due to shorter growth duration, it is essential to harness optimum heading date genes and ... ...

Abstract	Heading date is a critical agronomic trait that significantly affects grain yield and quality in rice. As early heading is typically associated with reduced yield due to shorter growth duration, it is essential to harness optimum heading date genes and their allelic combinations to promote heading while minimizing yield penalties. In this study, we identified quantitative trait loci (QTLs) for heading date and other major agronomic traits in a recombinant inbred line (RIL) population derived from a cross between Koshihikari and Baegilmi. Analyses on 3 major QTLs for heading date and their underlying genes (Hd1, Hd16, and Ghd7) revealed their pleiotropic effects on culm length, panicle length, and head rice percentage. Additionally, Ghd7 exhibited pleiotropic effects on panicle number and grain size. Among 8 different types of allelic combinations of the 3 heading date genes, RILs carrying a single nonfunctional hd16 or ghd7 under the functional background of the other 2 genes (Hd1hd16Ghd7 and Hd1Hd16ghd7) showed potential for maintaining yield and quality-related traits while accelerating heading. These results provide valuable insights for fine-tuning heading dates in rice breeding programs.
MeSH term(s)	Oryza/genetics ; Plant Breeding ; Phenotype ; Quantitative Trait Loci ; Alleles
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkad300
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Article ; Online: Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.

Kang, Hyeon Ju / Truong Hoang, Quan / Min, Jun / Son, Min Soo / Tram, Le Thi Hong / Kim, Byoung Choul / Song, Youngjun / Shim, Min Suk

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations ...

Abstract	Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations in sonosensitizers, especially their low aqueous stability and poor cellular uptake. In this study, non-ionic polysorbate (Tween 80, T80) was adopted to formulate effective nanocarriers for the safe and efficient delivery of sonosensitizers to cancer cells. Mitochondria-targeting triphenylphosphonium (TPP)-conjugated chlorin e6 (Ce6) sonosensitizer was loaded into T80-based micelles for efficient SDT. Pro-oxidant piperlongumine (PL) was co-encapsulated with TPP-conjugated Ce6 (T-Ce6) in T80 micelles to enable combination chemo-SDT. T80 micelles substantially enhanced the cellular internalization of T-Ce6. As a result, T80 micelles loaded with T-Ce6 and PL [T80(T-Ce6/PL)] significantly elevated intracellular reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells upon US exposure. Moreover, T-Ce6 exhibited selective accumulation within the mitochondria, leading to efficient cell death under US irradiation. Importantly, T80(T-Ce6/PL) micelles caused cancer-specific cell death by selectively triggering apoptosis in cancer cells through PL. This study demonstrated the feasibility of using T80(T-Ce6/PL) micelles for efficient and cancer-specific combination chemo-SDT.
MeSH term(s)	Humans ; Polysorbates ; Cell Line, Tumor ; Micelles ; Reactive Oxygen Species/metabolism ; Mitochondria/metabolism ; Porphyrins/metabolism ; Nanoparticles ; Neoplasms/drug therapy ; Organophosphorus Compounds
Chemical Substances	Polysorbates ; Micelles ; triphenylphosphonium ; Reactive Oxygen Species ; Porphyrins ; Organophosphorus Compounds
Language	English
Publishing date	2024-03-20
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/ijms25063474
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Article ; Online: Early onset senescence and cognitive impairment in a murine model of repeated mTBI.

Schwab, Nicole / Ju, YoungJun / Hazrati, Lili-Naz

Acta neuropathologica communications

2021 Volume 9, Issue 1, Page(s) 82

Abstract: Mild traumatic brain injury (mTBI) results in broad neurological symptoms and an increased risk of being diagnosed with a neurodegenerative disease later in life. While the immediate oxidative stress response and post-mortem pathology of the injured ... ...

Abstract	Mild traumatic brain injury (mTBI) results in broad neurological symptoms and an increased risk of being diagnosed with a neurodegenerative disease later in life. While the immediate oxidative stress response and post-mortem pathology of the injured brain has been well studied, it remains unclear how early pathogenic changes may drive persistent symptoms and confer susceptibility to neurodegeneration. In this study we have used a mouse model of repeated mTBI (rmTBI) to identify early gene expression changes at 24 h or 7 days post-injury (7 dpi). At 24 h post-injury, gene expression of rmTBI mice shows activation of the DNA damage response (DDR) towards double strand DNA breaks, altered calcium and cell-cell signalling, and inhibition of cell death pathways. By 7 dpi, rmTBI mice had a gene expression signature consistent with induction of cellular senescence, activation of neurodegenerative processes, and inhibition of the DDR. At both timepoints gliosis, microgliosis, and axonal damage were evident in the absence of any gross lesion, and by 7 dpi rmTBI also mice had elevated levels of IL1β, p21, 53BP1, DNA2, and p53, supportive of DNA damage-induced cellular senescence. These gene expression changes reflect establishment of processes usually linked to brain aging and suggests that cellular senescence occurs early and most likely prior to the accumulation of toxic proteins. These molecular changes were accompanied by spatial learning and memory deficits in the Morris water maze. To conclude, we have identified DNA damage-induced cellular senescence as a repercussion of repeated mild traumatic brain injury which correlates with cognitive impairment. Pathways involved in senescence may represent viable treatment targets of post-concussive syndrome. Senescence has been proposed to promote neurodegeneration and appears as an effective target to prevent long-term complications of mTBI, such as chronic traumatic encephalopathy and other related neurodegenerative pathologies.
MeSH term(s)	Age of Onset ; Aging/genetics ; Aging/pathology ; Aging/psychology ; Animals ; Brain Concussion/genetics ; Brain Concussion/pathology ; Brain Concussion/psychology ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/pathology ; Cognitive Dysfunction/psychology ; DNA Damage/physiology ; Disease Models, Animal ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL
Language	English
Publishing date	2021-05-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-021-01190-x
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Article ; Online: Discovery of E3 Ligase Ligands for Target Protein Degradation.

Lee, Jaeseok / Lee, Youngjun / Jung, Young Mee / Park, Ju Hyun / Yoo, Hyuk Sang / Park, Jongmin

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 19

Abstract: Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient ... ...

Abstract	Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligands have been mostly limited to either CRBN or VHL ligands. Those PROTACs showed their limitation due to the cell type specific expression of E3 ligases and recently reported resistance toward PROTACs with CRBN ligands or VHL ligands. To overcome these hurdles, the discovery of various E3 ligase ligands has been spotlighted to improve the current PROTAC technology. This review focuses on currently reported E3 ligase ligands and their application in the development of PROTACs.
MeSH term(s)	Ligands ; Proteins/metabolism ; Proteolysis ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Ligands ; Proteins ; Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-10-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27196515
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Article ; Online: Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells

YoungJun Ju / Yaacov Ben-David / Daniela Rotin / Eldad Zacksenhaus

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 15

Abstract: Abstract The eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, ... ...

Abstract	Abstract The eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, the contexts in which eEF2K inhibition is essential in TNBC and its consequences on the proteome are largely unknown. Here we show that genetic or pharmacological inhibition of eEF2K cooperated with glutamine (Gln) starvation, and synergized with glutaminase (GLS1) inhibitors to suppress growth of diverse TNBC cell lines. eEF2K inhibition also synergized with depletion of eukaryotic translation initiation factor 4E-binding protein 1 (eIF4EBP1; 4EBP1), a suppressor of eukaryotic protein translation initiation factor 4E (eIF4E), to induce c-MYC and Cyclin D1 expression, yet attenuate growth of TNBC cells. Proteomic analysis revealed that whereas eEF2K depletion alone uniquely induced Cyclin Dependent Kinase 1 (CDK1) and 6 (CDK6), combined depletion of eEF2K and 4EBP1 resulted in overlapping effects on the proteome, with the highest impact on the ‘Collagen containing extracellular matrix’ pathway (e.g. COL1A1), as well as the amino-acid transporter, SLC7A5/LAT1, suggesting a regulatory loop via mTORC1. In addition, combined depletion of eEF2K and 4EBP1 indirectly reduced the levels of IFN-dependent innate immune response-related factors. Thus, eEF2K inhibition triggers cell cycle arrest/death under unfavourable metabolic conditions such as Gln-starvation/GLS1 inhibition or 4EBP1 depletion, uncovering new therapeutic avenues for TNBC and underscoring a pressing need for clinically relevant eEF2K inhibitors.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Reducing contact resistance of MoS2-based field effect transistors through uniform interlayer insertion via atomic layer deposition.

Woo, Whang Je / Seo, Seunggi / Yoon, Hwi / Lee, Sanghun / Kim, Donghyun / Park, Seonyeong / Kim, Youngjun / Sohn, Inkyu / Park, JuSang / Chung, Seung-Min / Kim, Hyungjun

The Journal of chemical physics

2024 Volume 160, Issue 10

Abstract: Molybdenum disulfide (MoS2), a semiconducting two-dimensional layered transition metal dichalcogenide (2D TMDC), with attractive properties enables the opening of a new electronics era beyond Si. However, the notoriously high contact resistance (RC) ... ...

Abstract	Molybdenum disulfide (MoS2), a semiconducting two-dimensional layered transition metal dichalcogenide (2D TMDC), with attractive properties enables the opening of a new electronics era beyond Si. However, the notoriously high contact resistance (RC) regardless of the electrode metal has been a major challenge in the practical applications of MoS2-based electronics. Moreover, it is difficult to lower RC because the conventional doping technique is unsuitable for MoS2 due to its ultrathin nature. Therefore, the metal-insulator-semiconductor (MIS) architecture has been proposed as a method to fabricate a reliable and stable contact with low RC. Herein, we introduce a strategy to fabricate MIS contact based on atomic layer deposition (ALD) to dramatically reduce the RC of single-layer MoS2 field effect transistors (FETs). We utilize ALD Al2O3 as an interlayer for the MIS contact of bottom-gated MoS2 FETs. Based on the Langmuir isotherm, the uniformity of ALD Al2O3 films on MoS2 can be increased by modulating the precursor injection pressures even at low temperatures of 150 °C. We discovered, for the first time, that film uniformity critically affects RC without altering the film thickness. Additionally, we can add functionality to the uniform interlayer by adopting isopropyl alcohol (IPA) as an oxidant. Tunneling resistance across the MIS contact is lowered by n-type doping of MoS2 induced by IPA as the oxidant in the ALD process. Through a highly uniform interlayer combined with strong doping, the contact resistance is improved by more than two orders of magnitude compared to that of other MoS2 FETs fabricated in this study.
Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0196668
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Article ; Online: Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells.

Ju, YoungJun / Ben-David, Yaacov / Rotin, Daniela / Zacksenhaus, Eldad

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9181

Abstract: The eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, the ... ...

Abstract	The eukaryotic elongation factor-2 kinase, eEF2K, which restricts protein translation elongation, has been identified as a potential therapeutic target for diverse types of malignancies including triple negative breast cancer (TNBC). However, the contexts in which eEF2K inhibition is essential in TNBC and its consequences on the proteome are largely unknown. Here we show that genetic or pharmacological inhibition of eEF2K cooperated with glutamine (Gln) starvation, and synergized with glutaminase (GLS1) inhibitors to suppress growth of diverse TNBC cell lines. eEF2K inhibition also synergized with depletion of eukaryotic translation initiation factor 4E-binding protein 1 (eIF4EBP1; 4EBP1), a suppressor of eukaryotic protein translation initiation factor 4E (eIF4E), to induce c-MYC and Cyclin D1 expression, yet attenuate growth of TNBC cells. Proteomic analysis revealed that whereas eEF2K depletion alone uniquely induced Cyclin Dependent Kinase 1 (CDK1) and 6 (CDK6), combined depletion of eEF2K and 4EBP1 resulted in overlapping effects on the proteome, with the highest impact on the 'Collagen containing extracellular matrix' pathway (e.g. COL1A1), as well as the amino-acid transporter, SLC7A5/LAT1, suggesting a regulatory loop via mTORC1. In addition, combined depletion of eEF2K and 4EBP1 indirectly reduced the levels of IFN-dependent innate immune response-related factors. Thus, eEF2K inhibition triggers cell cycle arrest/death under unfavourable metabolic conditions such as Gln-starvation/GLS1 inhibition or 4EBP1 depletion, uncovering new therapeutic avenues for TNBC and underscoring a pressing need for clinically relevant eEF2K inhibitors.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Benzeneacetamides/administration & dosage ; Benzeneacetamides/pharmacology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cyclin D1/metabolism ; Cyclopentanes/pharmacology ; Drug Synergism ; Elongation Factor 2 Kinase/antagonists & inhibitors ; Elongation Factor 2 Kinase/genetics ; Female ; Gene Silencing ; Glutaminase/antagonists & inhibitors ; Humans ; Protein Kinase Inhibitors/pharmacology ; Proteins/analysis ; Proteins/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Sulfides/administration & dosage ; Sulfides/pharmacology ; Thiadiazoles/administration & dosage ; Thiadiazoles/pharmacology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	Adaptor Proteins, Signal Transducing ; Benzeneacetamides ; CB-839 ; CCND1 protein, human ; Cell Cycle Proteins ; Cyclopentanes ; EIF4EBP1 protein, human ; Protein Kinase Inhibitors ; Proteins ; Proto-Oncogene Proteins c-myc ; Sulfides ; TX1918 ; Thiadiazoles ; bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide ; Cyclin D1 (136601-57-5) ; EEF2K protein, human (EC 2.7.1.17) ; Elongation Factor 2 Kinase (EC 2.7.11.20) ; GLS protein, human (EC 3.5.1.2) ; Glutaminase (EC 3.5.1.2)
Language	English
Publishing date	2021-04-28
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/s41598-021-88816-1
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Article: Thioredoxin 1 regulation of protein

Ju, Youngjun / Wu, Lingyun / Yang, Guangdong

Biochemistry and biophysics reports

2015 Volume 5, Page(s) 27–34

Abstract: The importance of ... ...

Abstract	The importance of H
Language	English
Publishing date	2015-11-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2831046-9
ISSN	2405-5808
ISSN	2405-5808
DOI	10.1016/j.bbrep.2015.11.012
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Article: Projected lifetime cancer risk from cone-beam computed tomography for orthodontic treatment.

Jha, Nayansi / Kim, Yoon-Ji / Lee, Youngjun / Lee, Ju Young / Lee, Won Jin / Sung, Sang-Jin

Korean journal of orthodontics

2021 Volume 51, Issue 3, Page(s) 189–198

Abstract: Objective: To estimate the projected cancer risk attributable to diagnostic cone-beam computed tomography (CBCT) performed under different exposure settings for orthodontic purposes in children and adults.: Methods: We collected a list of CBCT ... ...

Abstract	Objective: To estimate the projected cancer risk attributable to diagnostic cone-beam computed tomography (CBCT) performed under different exposure settings for orthodontic purposes in children and adults. Methods: We collected a list of CBCT machines and their specifications from 38 orthodontists. Organ doses were estimated using median and maximum exposure settings of 105 kVp/156.8 mAs and 130 kVp/200 mAs, respectively. The projected cancer risk attributable to CBCT procedures performed 1-3 times within 2 years was calculated for children (aged 5 and 10 years) and adult (aged 20, 30, and 40 years) male and female patients. Results: For maximum exposure settings, the mean lifetime fractional ratio (LFR) was 14.28% for children and 0.91% for adults; this indicated that the risk to children was 16 times the risk to adults. For median exposure settings, the mean LFR was 5.25% and 0.58% for children and adults, respectively. The risk of cancer decreased with increasing age. For both median and maximum exposure settings, females showed a higher risk of cancer than did males in all age groups. Cancer risk increased with an increase in the frequency of CBCT procedures within a given period. Conclusions: The projected dental CBCT-associated cancer risk spans over a wide range depending on the machine parameters and image acquisition settings. Children and female patients are at a higher risk of developing cancer associated with diagnostic CBCT. Therefore, the use of diagnostic CBCT should be justified, and protective measures should be taken to minimize the harmful biological effects of radiation.
Language	English
Publishing date	2021-05-13
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2888152-7
ISSN	2234-7518 ; 2234-7518 ; 1225-5610
ISSN (online)	2234-7518
ISSN	2234-7518 ; 1225-5610
DOI	10.4041/kjod.2021.51.3.189
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Article: Metal-Halide Perovskite Design for Next-Generation Memories: First-Principles Screening and Experimental Verification.

Jung, Ju-Hyun / Kim, Seong Hun / Park, Youngjun / Lee, Donghwa / Lee, Jang-Sik

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2020 Volume 7, Issue 16, Page(s) 2001367

Abstract: Memory devices have been advanced so much, but still it is highly required to find stable and reliable materials with low-power consumption. Halide perovskites (HPs) have been recently adopted for memory application since they have advantages of fast ... ...

Abstract	Memory devices have been advanced so much, but still it is highly required to find stable and reliable materials with low-power consumption. Halide perovskites (HPs) have been recently adopted for memory application since they have advantages of fast switching based on ionic motion in crystal structure. However, HPs also suffer from poor stability, so it is necessary to improve the stability of HPs. In this regard, combined first-principles screening and experimental verification are performed to design HPs that have high environmental stability and low-operating voltage for memory devices. First-principles screening identifies 2D layered AB
Language	English
Publishing date	2020-06-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202001367
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