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Article ; Online: Non-random distribution of vacuoles in Schizosaccharomyces pombe.

Chadwick, William L / Biswas, Sujoy K / Bianco, Simone / Chan, Yee-Hung M

2020 Volume 17, Issue 6, Page(s) 65004

Abstract: A central question in eukaryotic cell biology asks, during cell division, how is the growth and distribution of organelles regulated to ensure each daughter cell receives an appropriate amount. For vacuoles in budding yeast, there are well described ... ...

Abstract	A central question in eukaryotic cell biology asks, during cell division, how is the growth and distribution of organelles regulated to ensure each daughter cell receives an appropriate amount. For vacuoles in budding yeast, there are well described organelle-to-cell size scaling trends as well as inheritance mechanisms involving highly coordinated movements. It is unclear whether such mechanisms are necessary in the symmetrically dividing fission yeast, Schizosaccharomyces pombe, in which random partitioning may be utilized to distribute vacuoles to daughter cells. To address the increasing need for high-throughput analysis, we are augmenting existing semi-automated image processing by developing fully automated machine learning methods for locating vacuoles and segmenting fission yeast cells from brightfield and fluorescence micrographs. All strains studied show qualitative correlations in vacuole-to-cell size scaling trends, i.e. vacuole volume, surface area, and number all increase with cell size. Furthermore, increasing vacuole number was found to be a consistent mechanism for the increase in total vacuole size in the cell. Vacuoles are not distributed evenly throughout the cell with respect to available cytoplasm. Rather, vacuoles show distinct peaks in distribution close to the nucleus, and this preferential localization was confirmed in mutants in which nucleus position is perturbed. Disruption of microtubules leads to quantitative changes in both vacuole size scaling trends and distribution patterns, indicating the microtubule cytoskeleton is a key mechanism for maintaining vacuole structure.
MeSH term(s)	Schizosaccharomyces/cytology ; Vacuoles/metabolism
Language	English
Publishing date	2020-10-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2133216-2
ISSN	1478-3975 ; 1478-3967
ISSN (online)	1478-3975
ISSN	1478-3967
DOI	10.1088/1478-3975/aba510
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Article ; Online: How cells know the size of their organelles.

Chan, Yee-Hung M / Marshall, Wallace F

Science (New York, N.Y.)

2012 Volume 337, Issue 6099, Page(s) 1186–1189

Abstract: Cells have developed ways to sense and control the size of their organelles. Size-sensing mechanisms range from direct measurements provided by dedicated reporters to indirect functional readouts, and they are used to modify organelle size under both ... ...

Abstract	Cells have developed ways to sense and control the size of their organelles. Size-sensing mechanisms range from direct measurements provided by dedicated reporters to indirect functional readouts, and they are used to modify organelle size under both normal and stress conditions. Organelle size can also be controlled in the absence of an identifiable size sensor. Studies on flagella have dissected principles of size sensing and control, and it will be exciting to see how these principles apply to other organelles.
MeSH term(s)	Animals ; Biological Transport ; Cell Physiological Phenomena ; Flagella/metabolism ; Flagella/physiology ; Flagella/ultrastructure ; Humans ; Models, Biological ; Organelle Size ; Organelles/chemistry ; Organelles/metabolism ; Organelles/ultrastructure
Language	English
Publishing date	2012-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1223539
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Article ; Online: Organelle Size Scaling of the Budding Yeast Vacuole by Relative Growth and Inheritance.

Chan, Yee-Hung M / Reyes, Lorena / Sohail, Saba M / Tran, Nancy K / Marshall, Wallace F

Current biology : CB

2016 Volume 26, Issue 9, Page(s) 1221–1228

Abstract: It has long been noted that larger animals have larger organs compared to smaller animals of the same species, a phenomenon termed scaling [1]. Julian Huxley proposed an appealingly simple model of "relative growth"-in which an organ and the whole body ... ...

Abstract	It has long been noted that larger animals have larger organs compared to smaller animals of the same species, a phenomenon termed scaling [1]. Julian Huxley proposed an appealingly simple model of "relative growth"-in which an organ and the whole body grow with their own intrinsic rates [2]-that was invoked to explain scaling in organs from fiddler crab claws to human brains. Because organ size is regulated by complex, unpredictable pathways [3], it remains unclear whether scaling requires feedback mechanisms to regulate organ growth in response to organ or body size. The molecular pathways governing organelle biogenesis are simpler than organogenesis, and therefore organelle size scaling in the cell provides a more tractable case for testing Huxley's model. We ask the question: is it possible for organelle size scaling to arise if organelle growth is independent of organelle or cell size? Using the yeast vacuole as a model, we tested whether mutants defective in vacuole inheritance, vac8Δ and vac17Δ, tune vacuole biogenesis in response to perturbations in vacuole size. In vac8Δ/vac17Δ, vacuole scaling increases with the replicative age of the cell. Furthermore, vac8Δ/vac17Δ cells continued generating vacuole at roughly constant rates even when they had significantly larger vacuoles compared to wild-type. With support from computational modeling, these results suggest there is no feedback between vacuole biogenesis rates and vacuole or cell size. Rather, size scaling is determined by the relative growth rates of the vacuole and the cell, thus representing a cellular version of Huxley's model.
Language	English
Publishing date	2016-05-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2016.03.020
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Article: How Cells Know the Size of Their Organelles

Chan, Yee-Hung M / Marshall, Wallace F

Science. 2012 Sept. 7, v. 337, no. 6099

2012

Abstract: ... understood, but an understanding is vital for interpreting normal cell function. Chan and Marshall (p. 1186 ...

Abstract	Sensing Cell Size How cells sense and control the size of their constituent parts is poorly understood, but an understanding is vital for interpreting normal cell function. Chan and Marshall (p. 1186) discuss how cells can sense and regulate the size of their internal structures or organelles. For example, bacterial flagellae act as their own tape measures. In eukaryote cells, reporter molecules may monitor cell and telomere length, and in molecular scaffolds, conformational changes and occupancy times measure organelle size. Indirect size selection may arise from a loss of function with growth or scaling problems with processes like intracellular transport. Now, advances in imaging offer glimpses into the mechanisms of cell sizing and the consequences if this process goes wrong.
Keywords	eukaryotic cells ; image analysis ; organelles ; telomeres
Language	English
Dates of publication	2012-0907
Size	p. 1186-1189.
Publishing place	American Association for the Advancement of Science
Document type	Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1223539
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Article ; Online: Scaling properties of cell and organelle size.

Chan, Yee-Hung M / Marshall, Wallace F

Organogenesis

2010 Volume 6, Issue 2, Page(s) 88–96

Abstract: How size is controlled is a fundamental question in biology. In this review, we discuss the use of scaling relationships-for example, power-laws of the form y∝x(α)-to provide a framework for comparison and interpretation of size measurements. Such ... ...

Abstract	How size is controlled is a fundamental question in biology. In this review, we discuss the use of scaling relationships-for example, power-laws of the form y∝x(α)-to provide a framework for comparison and interpretation of size measurements. Such analysis can illustrate the biological and physical principles underlying observed trends, as has been proposed for the allometric dependence of metabolic rate or limb structure on organism mass. Techniques for measuring size at smaller length-scales continue to improve, leading to more data on the control of size in cells and organelles. Size scaling of these structures is expected to influence growth patterns, functional capacity and intracellular transport. Furthermore, organelles such as the nucleus, mitochondria and endoplasmic reticulum show widely varying morphologies that affect their scaling properties. We provide brief summaries of these issues for individual organelles, and conclude with a discussion on how to apply this concept to better understand the mechanisms of size control in the cellular environment.
MeSH term(s)	Animals ; Cell Biology ; Cell Size ; Humans ; Organelle Size
Language	English
Publishing date	2010-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2159583-5
ISSN	1555-8592 ; 1555-8592
ISSN (online)	1555-8592
ISSN	1555-8592
DOI	10.4161/org.6.2.11464
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Article ; Online: Lipid-anchored DNA mediates vesicle fusion as observed by lipid and content mixing.

Chan, Yee-Hung M / van Lengerich, Bettina / Boxer, Steven G

Biointerphases

2010 Volume 3, Issue 2, Page(s) FA17

Abstract: A general method for synthesizing 5(')- and 3(')-coupled DNA-lipid conjugates has been developed and employed in DNA-mediated vesicle fusion. Vesicles presenting complementary DNA fuse, resulting in both outer and inner leaflet mixing as well as content ... ...

Abstract	A general method for synthesizing 5(')- and 3(')-coupled DNA-lipid conjugates has been developed and employed in DNA-mediated vesicle fusion. Vesicles presenting complementary DNA fuse, resulting in both outer and inner leaflet mixing as well as content mixing. Fusion is maximized using 5(')- and 3(')-coupled DNA on opposite vesicle partners, rather than only 5(')-coupled DNA, showing the importance of DNA orientation to the process. Lipid and content mixing assays show a dependence of fusion kinetics on the sequence and average number of DNA per vesicle. Vesicles without DNA or presenting noncomplementary sequences also appear to undergo some degree of lipid mixing or exchange, but no content mixing. Total lipid mixing appears to occur more efficiently than inner leaflet mixing and content mixing, and this may be explained by the observed nonspecific lipid mixing and/or the rise of a hemifused intermediate. The ability to control DNA sequence and the relative experimental simplicity of this system make it highly attractive to probe fundamental questions of membrane fusion using both ensemble and single vesicle assays.
Language	English
Publishing date	2010-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2234510-3
ISSN	1559-4106 ; 1934-8630
ISSN (online)	1559-4106
ISSN	1934-8630
DOI	10.1116/1.2889062
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Article: Model membrane systems and their applications.

Chan, Yee-Hung M / Boxer, Steven G

Current opinion in chemical biology

2007 Volume 11, Issue 6, Page(s) 581–587

Abstract: The complexity of biological membranes has motivated the development of a wide variety of simpler model systems whose size, geometry, and composition can be tailored with great precision. Approaches highlighted in this review are illustrated in Figure 1 ... ...

Abstract	The complexity of biological membranes has motivated the development of a wide variety of simpler model systems whose size, geometry, and composition can be tailored with great precision. Approaches highlighted in this review are illustrated in Figure 1 including vesicles, supported bilayers, and hybrid membrane systems. These have been used to study problems ranging from phase behavior to membrane fusion. Experimental membrane models continue to advance in complexity with respect to architecture, size, and composition, as do computer simulations of their properties and dynamics. Analytical techniques such as imaging secondary ion mass spectrometry have also been developed and refined to give increasing spatial resolution and information content on membrane composition and dynamics.
MeSH term(s)	Computer Simulation ; Lipid Bilayers ; Membranes, Artificial ; Models, Biological ; Unilamellar Liposomes
Chemical Substances	Lipid Bilayers ; Membranes, Artificial ; Unilamellar Liposomes
Language	English
Publishing date	2007-11-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2007.09.020
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Article ; Online: Kinetics of DNA-mediated docking reactions between vesicles tethered to supported lipid bilayers.

Chan, Yee-Hung M / Lenz, Peter / Boxer, Steven G

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

2007 Volume 104, Issue 48, Page(s) 18913–18918

Abstract: Membrane-membrane recognition and binding are crucial in many biological processes. We report an approach to studying the dynamics of such reactions by using DNA-tethered vesicles as a general scaffold for displaying membrane components. This system was ... ...

Abstract	Membrane-membrane recognition and binding are crucial in many biological processes. We report an approach to studying the dynamics of such reactions by using DNA-tethered vesicles as a general scaffold for displaying membrane components. This system was used to characterize the docking reaction between two populations of tethered vesicles that display complementary DNA. Deposition of vesicles onto a supported lipid bilayer was performed by using a microfluidic device to prevent mixing of the vesicles in bulk during sample preparation. Once tethered onto the surface, vesicles mixed via two-dimensional diffusion. DNA-mediated docking of two reacting vesicles results in their colocalization after collision and their subsequent tandem motion. Individual docking events and population kinetics were observed via epifluorescence microscopy. A lattice-diffusion simulation was implemented to extract from experimental data the probability, P(dock), that a collision leads to docking. For individual vesicles displaying small numbers of docking DNA, P(dock) shows a first-order relationship with copy number as well as a strong dependence on the DNA sequence. Both trends are explained by a model that includes both tethered vesicle diffusion on the supported bilayer and docking DNA diffusion over each vesicle's surface. These results provide the basis for the application of tethered vesicles to study other membrane reactions including protein-mediated docking and fusion.
MeSH term(s)	DNA, Complementary/chemistry ; DNA, Complementary/metabolism ; Diffusion ; Kinetics ; Lipid Bilayers/chemistry ; Microfluidic Analytical Techniques ; Microscopy, Fluorescence ; Models, Chemical ; Motion ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry ; Oligodeoxyribonucleotides/metabolism
Chemical Substances	DNA, Complementary ; Lipid Bilayers ; Oligodeoxyribonucleotides
Language	English
Publishing date	2007-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0706114104
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Article ; Online: Effects of linker sequences on vesicle fusion mediated by lipid-anchored DNA oligonucleotides.

Chan, Yee-Hung M / van Lengerich, Bettina / Boxer, Steven G

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

2009 Volume 106, Issue 4, Page(s) 979–984

Abstract: Synthetic lipid-oligonucleotide conjugates inserted into lipid vesicles mediate fusion when one population of vesicles displays the 5'-coupled conjugate and the other the 3'-coupled conjugate, so that anti-parallel hybridization allows the membrane ... ...

Abstract	Synthetic lipid-oligonucleotide conjugates inserted into lipid vesicles mediate fusion when one population of vesicles displays the 5'-coupled conjugate and the other the 3'-coupled conjugate, so that anti-parallel hybridization allows the membrane surfaces to come into close proximity. Improved assays show that lipid mixing proceeds more quickly and to a much greater extent than content mixing, suggesting the latter is rate limiting. To test the effect of membrane-membrane spacing on fusion, a series of conjugates was constructed by adding 2-24 noncomplementary bases at the membrane-proximal ends of two complementary sequences. Increasing linker lengths generally resulted in progressively reduced rates and extents of lipid and content mixing, in contrast to higher vesicle docking rates. The relatively flexible, single-stranded DNA linker facilitates docking but allows greater spacing between the vesicles after docking, thus making the transition into fusion less probable, but not preventing it altogether. These experiments demonstrate the utility of DNA as a model system for fusion proteins, where sequence can easily be modified to systematically probe the effect of distance between bilayers in the fusion reaction.
MeSH term(s)	Base Sequence ; DNA/genetics ; DNA/metabolism ; Lipid Bilayers/metabolism ; Lipids/chemistry ; Membrane Fusion ; Models, Biological ; Molecular Sequence Data ; Oligonucleotides/genetics ; Oligonucleotides/metabolism ; Organophosphorus Compounds ; SNARE Proteins/metabolism
Chemical Substances	Lipid Bilayers ; Lipids ; Oligonucleotides ; Organophosphorus Compounds ; SNARE Proteins ; phosphoramidite ; DNA (9007-49-2)
Language	English
Publishing date	2009-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0812356106
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Article ; Online: Review on the screening of urine glucose for early diagnosis of type 2 diabetes mellitus in school children and adolescents with obesity in Hong Kong.

Pang, Gloria Shir-Wey / Chung, Thomas Wai-Hung / Choy, Heather Hiu-Ting / Lee, Ching-Yin / Tung, Joanna Yuet-Ling / Fu, Antony Chun-Cheung / Tsang, Jennifer Wing-Yan / Yau, Ho-Chung / Belaramani, Kiran M / Wong, Lap-Ming / But, Betty Wai-Man / Chow, Jasmine Chi-Kwan / Wong, Shirley Man-Yee / Cheung, Patrick Chi-Hung / Lo, Priscilla Wai-Chee / Ng, Kwok-Leung / Poon, Sarah Wing-Yiu / Chan, Kwong Tat / Chan, Angela Mo-Kit /

Wong, Sammy Wai-Chun / Tay, Ming-Kut / Chung, Ying-Ki / Lam, Yuen-Yu / Kwan, Elaine Yin-Wah

Journal of pediatric endocrinology & metabolism : JPEM

2024 Volume 37, Issue 2, Page(s) 130–136

Abstract: Objectives: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students ...

Abstract	Objectives: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. Methods: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. Results: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. Conclusions: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA
MeSH term(s)	Male ; Female ; Adolescent ; Humans ; Child ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Hong Kong/epidemiology ; Pediatric Obesity ; Glucose ; Diabetes Complications ; Early Diagnosis
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-01-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1231070-0
ISSN	2191-0251 ; 0334-018X
ISSN (online)	2191-0251
ISSN	0334-018X
DOI	10.1515/jpem-2023-0295
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