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  • 1
    Publication Date: 2007-08-11
    Description: Tricyclic antidepressants exert their pharmacological effect-inhibiting the reuptake of serotonin, norepinephrine, and dopamine-by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711652/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711652/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Zheng -- Zhen, Juan -- Karpowich, Nathan K -- Goetz, Regina M -- Law, Christopher J -- Reith, Maarten E A -- Wang, Da-Neng -- DA013261/DA/NIDA NIH HHS/ -- DA019676/DA/NIDA NIH HHS/ -- GM075026/GM/NIGMS NIH HHS/ -- GM075936/GM/NIGMS NIH HHS/ -- R01 DA013261/DA/NIDA NIH HHS/ -- R01 DA019676/DA/NIDA NIH HHS/ -- R01 DK053973/DK/NIDDK NIH HHS/ -- R21 DK060841/DK/NIDDK NIH HHS/ -- R21 GM075936/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM095315/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 7;317(5843):1390-3. Epub 2007 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17690258" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antidepressive Agents, Tricyclic/chemistry/*metabolism ; Bacterial Proteins/chemistry/*metabolism ; Binding Sites ; Caenorhabditis elegans Proteins/chemistry/metabolism ; Cell Line ; Conserved Sequence ; Crystallography, X-Ray ; Desipramine/chemistry/*metabolism ; Dopamine/chemistry/metabolism ; Dopamine Uptake Inhibitors/chemistry/metabolism ; Drosophila Proteins/chemistry/metabolism ; Humans ; Leucine/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Uptake Inhibitors/chemistry/*metabolism ; Norepinephrine/chemistry/metabolism ; Norepinephrine Plasma Membrane Transport Proteins/antagonists & ; inhibitors/chemistry/metabolism ; Plasma Membrane Neurotransmitter Transport Proteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Sequence Homology, Amino Acid ; Serotonin/chemistry/metabolism ; Serotonin Uptake Inhibitors/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2004-12-14
    Description: We report a draft sequence for the genome of the domesticated silkworm (Bombyx mori), covering 90.9% of all known silkworm genes. Our estimated gene count is 18,510, which exceeds the 13,379 genes reported for Drosophila melanogaster. Comparative analyses to fruitfly, mosquito, spider, and butterfly reveal both similarities and differences in gene content.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xia, Qingyou -- Zhou, Zeyang -- Lu, Cheng -- Cheng, Daojun -- Dai, Fangyin -- Li, Bin -- Zhao, Ping -- Zha, Xingfu -- Cheng, Tingcai -- Chai, Chunli -- Pan, Guoqing -- Xu, Jinshan -- Liu, Chun -- Lin, Ying -- Qian, Jifeng -- Hou, Yong -- Wu, Zhengli -- Li, Guanrong -- Pan, Minhui -- Li, Chunfeng -- Shen, Yihong -- Lan, Xiqian -- Yuan, Lianwei -- Li, Tian -- Xu, Hanfu -- Yang, Guangwei -- Wan, Yongji -- Zhu, Yong -- Yu, Maode -- Shen, Weide -- Wu, Dayang -- Xiang, Zhonghuai -- Yu, Jun -- Wang, Jun -- Li, Ruiqiang -- Shi, Jianping -- Li, Heng -- Li, Guangyuan -- Su, Jianning -- Wang, Xiaoling -- Li, Guoqing -- Zhang, Zengjin -- Wu, Qingfa -- Li, Jun -- Zhang, Qingpeng -- Wei, Ning -- Xu, Jianzhe -- Sun, Haibo -- Dong, Le -- Liu, Dongyuan -- Zhao, Shengli -- Zhao, Xiaolan -- Meng, Qingshun -- Lan, Fengdi -- Huang, Xiangang -- Li, Yuanzhe -- Fang, Lin -- Li, Changfeng -- Li, Dawei -- Sun, Yongqiao -- Zhang, Zhenpeng -- Yang, Zheng -- Huang, Yanqing -- Xi, Yan -- Qi, Qiuhui -- He, Dandan -- Huang, Haiyan -- Zhang, Xiaowei -- Wang, Zhiqiang -- Li, Wenjie -- Cao, Yuzhu -- Yu, Yingpu -- Yu, Hong -- Li, Jinhong -- Ye, Jiehua -- Chen, Huan -- Zhou, Yan -- Liu, Bin -- Wang, Jing -- Ye, Jia -- Ji, Hai -- Li, Shengting -- Ni, Peixiang -- Zhang, Jianguo -- Zhang, Yong -- Zheng, Hongkun -- Mao, Bingyu -- Wang, Wen -- Ye, Chen -- Li, Songgang -- Wang, Jian -- Wong, Gane Ka-Shu -- Yang, Huanming -- Biology Analysis Group -- 1 P50 HG02351/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1937-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Southwest Agricultural University, Chongqing Beibei, 400716, China. xiaqy@swau.cq.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591204" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Anopheles/genetics ; Body Patterning/genetics ; Bombyx/*genetics/growth & development/metabolism ; Butterflies/genetics ; Computational Biology ; DNA Transposable Elements ; Drosophila melanogaster/genetics ; Exocrine Glands/metabolism ; Expressed Sequence Tags ; Female ; Genes, Homeobox ; *Genes, Insect ; *Genome ; Immunity, Innate/genetics ; Insect Hormones/genetics ; Insect Proteins/genetics ; Male ; Molecular Sequence Data ; *Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Sex Determination Processes ; Spiders/genetics ; Wings, Animal/growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-03-18
    Description: The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore. The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4)(2) heterotetramer and are required for the deposition of CenH3 at centromeres in vivo. Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An alpha-helix and an irregular loop at the conserved amino terminus and a shorter alpha-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077455/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077455/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Zheng -- Feng, Hanqiao -- Zhou, Bing-Rui -- Ghirlando, Rodolfo -- Hu, Kaifeng -- Zwolak, Adam -- Miller Jenkins, Lisa M -- Xiao, Hua -- Tjandra, Nico -- Wu, Carl -- Bai, Yawen -- Z01 BC010808-01/Intramural NIH HHS/ -- England -- Nature. 2011 Apr 14;472(7342):234-7. doi: 10.1038/nature09854. Epub 2011 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21412236" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Autoantigens/chemistry/metabolism ; Binding Sites ; Centromere/*chemistry/metabolism ; Chromosomal Proteins, Non-Histone/*chemistry/*metabolism ; Conserved Sequence ; DNA/chemistry/metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Histones/chemistry/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Chaperones/chemistry/metabolism ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Nucleosomes/chemistry/metabolism ; Protein Binding ; Protein Conformation ; *Saccharomyces cerevisiae/cytology/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-02-06
    Description: Glutamate transporters terminate neurotransmission by clearing synaptically released glutamate from the extracellular space, allowing repeated rounds of signalling and preventing glutamate-mediated excitotoxicity. Crystallographic studies of a glutamate transporter homologue from the archaeon Pyrococcus horikoshii, GltPh, showed that distinct transport domains translocate substrates into the cytoplasm by moving across the membrane within a central trimerization scaffold. Here we report direct observations of these 'elevator-like' transport domain motions in the context of reconstituted proteoliposomes and physiological ion gradients using single-molecule fluorescence resonance energy transfer (smFRET) imaging. We show that GltPh bearing two mutations introduced to impart characteristics of the human transporter exhibits markedly increased transport domain dynamics, which parallels an increased rate of substrate transport, thereby establishing a direct temporal relationship between transport domain motion and substrate uptake. Crystallographic and computational investigations corroborated these findings by revealing that the 'humanizing' mutations favour structurally 'unlocked' intermediate states in the transport cycle exhibiting increased solvent occupancy at the interface between the transport domain and the trimeric scaffold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351760/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akyuz, Nurunisa -- Georgieva, Elka R -- Zhou, Zhou -- Stolzenberg, Sebastian -- Cuendet, Michel A -- Khelashvili, George -- Altman, Roger B -- Terry, Daniel S -- Freed, Jack H -- Weinstein, Harel -- Boudker, Olga -- Blanchard, Scott C -- 5U54GM087519/GM/NIGMS NIH HHS/ -- P01DA012408/DA/NIDA NIH HHS/ -- P41 GM103521/GM/NIGMS NIH HHS/ -- P41GM103521/GM/NIGMS NIH HHS/ -- R01 EB003150/EB/NIBIB NIH HHS/ -- R01 GM025862/GM/NIGMS NIH HHS/ -- R01 GM098859/GM/NIGMS NIH HHS/ -- R010EB003150/EB/NIBIB NIH HHS/ -- R01GM098859/GM/NIGMS NIH HHS/ -- R21MH099491/MH/NIMH NIH HHS/ -- R37 NS085318/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Feb 5;518(7537):68-73. doi: 10.1038/nature14158.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA. ; 1] National Biomedical Center for Advanced ESR Technology, Cornell University, Ithaca, New York 14853, USA [2] Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA. ; 1] Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Swiss Institute of Bioinformatics, Quartier Sorge - Batiment Genopode, 1015 Lausanne, Switzerland. ; 1] Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, Cornell University, 1305 York Avenue, New York, New York 10065, USA. ; 1] Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Tri-Institutional Training Program in Chemical Biology, 445 East 69th Street, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25652997" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems, Acidic/*chemistry/genetics/*metabolism ; Aspartic Acid/*metabolism ; Biological Transport ; Crystallography, X-Ray ; Detergents ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Ligands ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Movement ; Mutant Proteins/chemistry/genetics/metabolism ; Mutation/genetics ; Protein Stability ; Protein Structure, Tertiary ; Proteolipids/metabolism ; Pyrococcus horikoshii/*chemistry ; Sodium/metabolism ; Solvents ; Thermodynamics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 91 (1995), S. 481-488 
    ISSN: 1432-2242
    Keywords: Rice ; Oryza sativa ; DNA fingerprinting ; Minisatellites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A rice minisatellite probe detecting DNA fingerprints was used to assess genetic variation in cultivated rice (Oryza sativa L.). Fifty-seven cultivars of rice, including 40 closely related cultivars released in the US, were studied. Rice DNA fingerprinting revealed high levels of polymorphism among distantly related cultivars. The variability of fingerprinting pattern was reduced in the closely related cultivars. A genetic similarity index (S) was computed based on shared fragments between each pair of cultivars, and genetic distance (D) was used to construct the dendrograms depicting genetic relationships among rice cultivars. Cluster analysis of genetic distance tended to group rice cultivars into different units corresponding with their varietal types and breeding pedigrees. However, by comparison with the coefficients of parentage, the criterion of relatedness based on DNA fingerprints appeared to overestimate the genetic relationships between some of the closely related US cultivars. Although this may reduce the power of fingerprints for genetic analysis, we were able to demonstrate that DNA fingerprinting with minisatellite sequences is simpler and more sensitive than most other types of marker systems in detecting genetic variation in rice.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 95 (1997), S. 112-118 
    ISSN: 1432-2242
    Keywords: Key words Diallel cross ; Hybrid rice ; Oryza sativa ; Restriction fragment length polymorphism (RFLP) ; Simple sequence repeat (SSR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The partial sterility of hybrids between the indica and japonica rice subspecies of Asian cultivated rice is a serious constraint for utilizing inter-subspecific heterosis in hybrid rice breeding. In this study, we have investigated the relationship between molecular-marker polymorphism and indica-japonica hybrid fertility using a diallel set involving 20 rice accessions including 9 indica and 11 japonica varieties. Spikelet fertility of the resulting 190 F1s and their parents was examined in a replicated field trial. Intra-subspecific hybrids showed much higher spikelet fertility than inter-subspecific hybrids except in crosses involving wide-compatibility varieties. The parents were surveyed for DNA polymorphism using 96 RFLP and ten SSR markers, which revealed extensive genetic differentiation between indica and japonica varieties. A large number of markers detected highly significant effects on hybrid fertility. The chromosomal locations for many of the positive markers coincided well with previously identified loci for hybrid sterility. The correlation between hybrid fertility and parental distance was low in both intra- and inter-subspecific crosses. The results suggest that the genetic basis of indica-japonica hybrid sterility is complex. It is the qualitative, rather than the quantitative, difference between the parents that determines the fertility of hybrids.
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  • 7
    ISSN: 1573-5060
    Keywords: Oryza sativa ; inter-varietal cross ; spikelet fertility ; genetic basis ; rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary There is much interest in the inter-varietal fertility of Asian cultivated rice. In this study, we analyzed the fertility of hybrids in a diallel set of 210 crosses involving 21 parents representing a broad range of the cultivated rice germplasm including landraces, primitive cultivars, modern elite cultivars and parents of hybrid rice. The materials were also carefully selected with respect to indica-japonica classification including typical indica/japonica, more or less intermediate and wide compatibility varieties. The level of hybrid fertility varied widely among the crosses from almost completely sterile to fully fertile. In general, hybrid fertility of intra-subspecific crosses, i.e., indica by indica (I×I) and japonica by japonica (J×J), is much higher than inter-subspecific crosses (I×J or J×I). The fertility varied widely in hybrids involving wide compatibility varieties and also in inter-subspecific crosses not involving wide compatibility varieties. An analysis of variance showed that both the main effects of indica and japonica parents and the interaction between the parents are highly significant in determining hybrid fertility. We speculate that, in addition to wide compatibility, the overall genetic difference between the indica and japonica parents, that may involve a series of minor mutations, play an important role in determining the hybrid fertility. There are also genes of sizable effect that influence fertility in hybrids resulting from specific combinations of the parents.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Theoretical and applied genetics 93 (1996), S. 1218-1224 
    ISSN: 1432-2242
    Keywords: Oryza sativa ; Hybrid rice ; Predicting heterosis ; Diallel cross ; Restriction fragment length polymorphism (RFLP) ; Simple sequence repeat (SSR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An essential assumption underlying markerbased prediction of hybrid performance is a strong linear correlation between molecular marker heterozygosity and hybrid performance or heterosis. This study was intended to investigate the extent of the correlations between molecular marker heterozygosity and hybrid performance in crosses involving two sets of rice materials, 9 indica and 11 japonica varieties. These materials represent a broad spectrum of the cultivated rice gene pool including landraces, primitive cultivars, historically important cultivars, modern elite cultivars and parents of superior hybrids. Varieties within each set were intermated in all possible nonreciprocal pairs resulting in 36 crosses in the indica set and 55 in the japonica set. The F1s and their parents, 111 entries in total, were examined for performance of seven traits in a replicated field trial. The parents were surveyed for polymorphisms using 96 RFLP and ten SSR markers selected at regular intervals from a published molecular marker linkage map. Molecular marker genotypes of the F1 hybrids were deduced from the parental genotypes. The analysis showed that, with very few exceptions, correlations in the indica dataset were higher than in that of their japonica counterparts. Among the seven traits analyzed, plant height showed the highest correlation between heterozygosity and hybrid performance and heteorsis in both indica and japonica datasets. Correlations were low to intermediate between hybrid performance and heterozygosity (both general and specific) in yield and yield component traits in both indica and japonica sets, and also low to intermediate between specific heterozygosity and heterosis in the indica set, whereas very little correlation was detected between heterosis and heterozygosity (either general or specific) in the japonica set. In comparison to the results from our previous studies, we concluded that the relationship between molecular marker heterozygosity and heterosis is variable, depending on the genetic materials used in the study, the diversity of rice germplasms and the complexity of the genetic basis of heterosis.
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