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Article ; Online: Height matters-from monogenic disorders to normal variation.

Durand, Claudia / Rappold, Gudrun A

2013 Volume 9, Issue 3, Page(s) 171–177

Abstract: Height is a classic polygenic quantitative trait with a high level of heritability. As it is a simple and stable parameter to measure, height is a model for both common, complex disorders and monogenic, Mendelian disease. In this Review, we examine ... ...

Abstract	Height is a classic polygenic quantitative trait with a high level of heritability. As it is a simple and stable parameter to measure, height is a model for both common, complex disorders and monogenic, Mendelian disease. In this Review, we examine height from the perspective of monogenic and complex genetics and discuss the lessons learned so far. We explore several examples of rare sequence variants with large effects on height and compare these variants to the common variants identified in genome-wide association studies that have small effects on height. We discuss how copy number changes or genetic interactions might contribute to the unidentified aspects of the heritability of height. We also ask whether information derived from genome-wide association studies on specific loci in the vicinity of genes can be used for further research in clinical paediatric endocrinology. Furthermore, we address key challenges that remain for gene discovery and for the transition of moving from genomic localization to mechanistic insights, with an emphasis on using next-generation sequencing to identify causative variants of people at the extremes of height distribution.
MeSH term(s)	Body Height/genetics ; Fibrillins ; Genetic Variation/genetics ; Genome-Wide Association Study ; Growth/genetics ; Homeodomain Proteins/genetics ; Human Growth Hormone/genetics ; Humans ; Microfilament Proteins/genetics ; Multifactorial Inheritance ; Mutation ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Short Stature Homeobox Protein
Chemical Substances	Fibrillins ; Homeodomain Proteins ; Microfilament Proteins ; SHOX protein, human ; Short Stature Homeobox Protein ; Human Growth Hormone (12629-01-5) ; FGFR3 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
Language	English
Publishing date	2013-01-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/nrendo.2012.251
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Article ; Online: My Genome Belongs to Me

Deuber Dominic / Egger Christoph / Fech Katharina / Malavolta Giulio / Schröder Dominique / Thyagarajan Sri Aravinda Krishnan / Battke Florian / Durand Claudia

Proceedings on Privacy Enhancing Technologies, Vol 2019, Iss 1, Pp 108-

Controlling Third Party Computation on Genomic Data

2019 Volume 132

Abstract: An individual’s genetic information is possibly the most valuable personal information. While knowledge of a person’s DNA sequence can facilitate the diagnosis of several heritable diseases and allow personalized treatment, its exposure comes with ... ...

Abstract	An individual’s genetic information is possibly the most valuable personal information. While knowledge of a person’s DNA sequence can facilitate the diagnosis of several heritable diseases and allow personalized treatment, its exposure comes with significant threats to the patient’s privacy. Currently known solutions for privacy-respecting computation require the owner of the DNA to either be heavily involved in the execution of a cryptographic protocol or to completely outsource the access control to a third party. This motivates the demand for cryptographic protocols which enable computation over encrypted genomic data while keeping the owner of the genome in full control. We envision a scenario where data owners can exercise arbitrary and dynamic access policies, depending on the intended use of the analysis results and on the credentials of who is conducting the analysis. At the same time, data owners are not required to maintain a local copy of their entire genetic data and do not need to exhaust their computational resources in an expensive cryptographic protocol.
Keywords	secure multi-party computation ; protocols ; dna security ; genome privacy ; Ethics ; BJ1-1725 ; Electronic computers. Computer science ; QA75.5-76.95
Subject code	303 ; 005
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
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Article ; Online: SHOX triggers the lysosomal pathway of apoptosis via oxidative stress.

Hristov, Georgi / Marttila, Tiina / Durand, Claudia / Niesler, Beate / Rappold, Gudrun A / Marchini, Antonio

Human molecular genetics

2014 Volume 23, Issue 6, Page(s) 1619–1630

Abstract: The SHOX gene encodes for a transcription factor important for normal bone development. Mutations in the gene are associated with idiopathic short stature and are responsible for the growth failure and skeletal defects found in the majority of patients ... ...

Abstract	The SHOX gene encodes for a transcription factor important for normal bone development. Mutations in the gene are associated with idiopathic short stature and are responsible for the growth failure and skeletal defects found in the majority of patients with Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia. SHOX is expressed in growth plate chondrocytes where it is supposed to modulate the proliferation, differentiation and cell death of these cells. Supporting this hypothesis, in vitro studies have shown that SHOX expression induces cell cycle arrest and apoptosis in both transformed and primary cells. In this study, we further characterized the cell death mechanisms triggered by SHOX and compared them with the effects induced by one clinically relevant mutant form of SHOX, detected in LWD patients (SHOX R153L) and a SHOX C-terminally truncated version (L185X). We show that SHOX expression in U2OS osteosarcoma cells leads to oxidative stress that, in turn, induces lysosomal membrane rupture with release of active cathepsin B to the cytosol and subsequent activation of the intrinsic apoptotic pathway characterized by mitochondrial membrane permeabilization and caspase activation. Importantly, cells expressing SHOX R153L or L185X did not display any of these features. Given the fact that many of the events observed in SHOX-expressing cells also characterize the complex cell death process occurring in the growth plate during endochondral ossification, our findings further support the hypothesis that SHOX may play a central role in the regulation of the cell death pathways activated during long bone development.
MeSH term(s)	Apoptosis ; Caspases/metabolism ; Cathepsin B/metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Growth Disorders/genetics ; Growth Disorders/pathology ; Growth Plate/metabolism ; Homeodomain Proteins/metabolism ; Humans ; Lysosomes/genetics ; Lysosomes/metabolism ; Mutation ; Osteochondrodysplasias/genetics ; Osteochondrodysplasias/pathology ; Osteosarcoma/genetics ; Osteosarcoma/metabolism ; Oxidative Stress ; Short Stature Homeobox Protein
Chemical Substances	Homeodomain Proteins ; SHOX protein, human ; Short Stature Homeobox Protein ; Caspases (EC 3.4.22.-) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2014-03-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddt552
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Article ; Online: Controlling my genome with my smartphone: first clinical experiences of the PROMISE system.

Clinical research in cardiology : official journal of the German Cardiac Society

2021 Volume 111, Issue 6, Page(s) 638–650

Abstract: Background: The development of Precision Medicine strategies requires high-dimensional phenotypic and genomic data, both of which are highly privacy-sensitive data types. Conventional data management systems lack the capabilities to sufficiently handle ... ...

Abstract	Background: The development of Precision Medicine strategies requires high-dimensional phenotypic and genomic data, both of which are highly privacy-sensitive data types. Conventional data management systems lack the capabilities to sufficiently handle the expected large quantities of such sensitive data in a secure manner. PROMISE is a genetic data management concept that implements a highly secure platform for data exchange while preserving patient interests, privacy, and autonomy. Methods: The concept of PROMISE to democratize genetic data was developed by an interdisciplinary team. It integrates a sophisticated cryptographic concept that allows only the patient to grant selective access to defined parts of his genetic information with single DNA base-pair resolution cryptography. The PROMISE system was developed for research purposes to evaluate the concept in a pilot study with nineteen cardiomyopathy patients undergoing genotyping, questionnaires, and longitudinal follow-up. Results: The safety of genetic data was very important to 79%, and patients generally regarded the data as highly sensitive. More than half the patients reported that their attitude towards the handling of genetic data has changed after using the PROMISE app for 4 months (median). The patients reported higher confidence in data security and willingness to share their data with commercial third parties, including pharmaceutical companies (increase from 5 to 32%). Conclusion: PROMISE democratizes genomic data by a transparent, secure, and patient-centric approach. This clinical pilot study evaluating a genetic data infrastructure is unique and shows that patient's acceptance of data sharing can be increased by patient-centric decision-making.
MeSH term(s)	Computer Security ; Humans ; Information Dissemination ; Pilot Projects ; Privacy ; Smartphone
Language	English
Publishing date	2021-10-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2213295-8
ISSN	1861-0692 ; 1861-0684
ISSN (online)	1861-0692
ISSN	1861-0684
DOI	10.1007/s00392-021-01942-8
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Article ; Online: The homeobox transcription factor HOXA9 is a regulator of SHOX in U2OS cells and chicken micromass cultures.

Durand, Claudia / Decker, Eva / Roeth, Ralph / Schneider, Katja U / Rappold, Gudrun

PloS one

2012 Volume 7, Issue 9, Page(s) e45369

Abstract: The homeobox gene SHOX encodes for a transcription factor that plays an important role during limb development. Mutations or deletions of SHOX in humans cause short stature in Turner, Langer and Leri-Weill syndrome as well as idiopathic short stature. ... ...

Abstract	The homeobox gene SHOX encodes for a transcription factor that plays an important role during limb development. Mutations or deletions of SHOX in humans cause short stature in Turner, Langer and Leri-Weill syndrome as well as idiopathic short stature. During embryonic development, SHOX is expressed in a complex spatio-temporal pattern that requires the presence of specific regulatory mechanisms. Up to now, it was known that SHOX is regulated by two upstream promoters and several enhancers on either side of the gene, but no regulators have been identified that can activate or repress the transcription of SHOX by binding to these regulatory elements. We have now identified the homeodomain protein HOXA9 as a positive regulator of SHOX expression in U2OS cells. Using luciferase assays, chromatin immunoprecipitation and electrophoretic mobility shift assays, we could narrow down the HOXA9 binding site to two AT-rich sequences of 31 bp within the SHOX promoter 2. Virus-induced Hoxa9 overexpression in a chicken micromass model validated the regulation of Shox by Hoxa9 (negative regulation). As Hoxa9 and Shox are both expressed in overlapping regions of the developing limb buds, a regulatory relationship of Hoxa9 and Shox during the process of limb development can be assumed.
MeSH term(s)	Animals ; Binding Sites ; Cell Line, Tumor ; Chick Embryo ; Chickens ; Chromatin Immunoprecipitation ; CpG Islands/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Electrophoretic Mobility Shift Assay ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; In Situ Hybridization ; Myeloid Ecotropic Viral Integration Site 1 Protein ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Short Stature Homeobox Protein
Chemical Substances	DNA-Binding Proteins ; Homeodomain Proteins ; Myeloid Ecotropic Viral Integration Site 1 Protein ; Neoplasm Proteins ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins ; SHOX protein, human ; Short Stature Homeobox Protein ; homeobox protein HOXA9 ; PBX1 protein, human
Language	English
Publishing date	2012-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0045369
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Article ; Online: Enhancer elements upstream of the SHOX gene are active in the developing limb.

Durand, Claudia / Bangs, Fiona / Signolet, Jason / Decker, Eva / Tickle, Cheryll / Rappold, Gudrun

European journal of human genetics : EJHG

2009 Volume 18, Issue 5, Page(s) 527–532

Abstract: Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in ... ...

Abstract	Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.
MeSH term(s)	Animals ; Chick Embryo ; Chickens/genetics ; Chromosomes, Human, X/genetics ; Conserved Sequence/genetics ; DNA, Intergenic/genetics ; Enhancer Elements, Genetic/genetics ; Extremities/embryology ; Genetic Testing ; Genome, Human/genetics ; Homeodomain Proteins/genetics ; Humans ; Sequence Homology, Nucleic Acid ; Short Stature Homeobox Protein ; Telomere/genetics
Chemical Substances	DNA, Intergenic ; Homeodomain Proteins ; SHOX protein, human ; Short Stature Homeobox Protein
Language	English
Publishing date	2009-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/ejhg.2009.216
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Article ; Online: Alternative splicing and nonsense-mediated RNA decay contribute to the regulation of SHOX expression.

Durand, Claudia / Roeth, Ralph / Dweep, Harsh / Vlatkovic, Irena / Decker, Eva / Schneider, Katja Ute / Rappold, Gudrun

PloS one

2011 Volume 6, Issue 3, Page(s) e18115

Abstract: The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During ... ...

Abstract	The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3'UTR exons yielded insights into the putative role of the different 3'UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level.
MeSH term(s)	Alternative Splicing/genetics ; Binding Sites ; Codon, Nonsense/genetics ; Exons/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; RNA Stability/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Short Stature Homeobox Protein
Chemical Substances	Codon, Nonsense ; Homeodomain Proteins ; MicroRNAs ; Protein Isoforms ; RNA, Messenger ; SHOX protein, human ; Short Stature Homeobox Protein
Language	English
Publishing date	2011-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0018115
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Article ; Online: FGFR3 is a target of the homeobox transcription factor SHOX in limb development.

Decker, Eva / Durand, Claudia / Bender, Sebastian / Rödelsperger, Christian / Glaser, Anne / Hecht, Jochen / Schneider, Katja U / Rappold, Gudrun

Human molecular genetics

2011 Volume 20, Issue 8, Page(s) 1524–1535

Abstract: The short stature homeobox gene SHOX encodes a transcription factor which is important for normal limb development. In humans, SHOX deficiency has been associated with various short stature syndromes including Leri-Weill dyschondrosteosis (LWD), Langer ... ...

Abstract	The short stature homeobox gene SHOX encodes a transcription factor which is important for normal limb development. In humans, SHOX deficiency has been associated with various short stature syndromes including Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia and Turner syndrome as well as non-syndromic idiopathic short stature. A common feature of these syndromes is disproportionate short stature with a particular shortening of the forearms and lower legs. In our studies employing microarray analyses and cell culture experiments, we revealed a strong positive effect of SHOX on the expression of the fibroblast growth factor receptor gene FGFR3, another well-known factor for limb development. Luciferase reporter gene assays show that SHOX activates the extended FGFR3 promoter, and results from chromatin immunoprecipitation (ChIP)-sequencing, ChIP and electrophoretic mobility shift assay experiments suggest a direct binding of SHOX to multiple upstream sequences of FGFR3. To further investigate these regulations in a cellular system for limb development, the effect of viral overexpression of Shox in limb bud derived chicken micromass cultures was tested. We found that Fgfr3 was negatively regulated by Shox, as demonstrated by quantitative real-time polymerase chain reaction and in situ hybridization. This repressive effect might explain the almost mutually exclusive expression patterns of Fgfr3 and Shox in embryonic chicken limbs. A negative regulation that occurs mainly in the mesomelic segments, a region where SHOX is known to be strongly expressed, offers a possible explanation for the phenotypes seen in patients with FGFR3 (e.g. achondroplasia) and SHOX defects (e.g. LWD). In summary, these data present a link between two frequent short stature phenotypes.
MeSH term(s)	Animals ; Base Sequence ; Cell Line, Tumor ; Chick Embryo ; Chondrocytes/metabolism ; Down-Regulation ; Ectoderm/metabolism ; Genes, Reporter ; Hindlimb/cytology ; Hindlimb/embryology ; Hindlimb/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Luciferases, Firefly/biosynthesis ; Luciferases, Firefly/genetics ; Mesoderm/metabolism ; Molecular Sequence Data ; Mutation, Missense ; Phenotype ; Promoter Regions, Genetic ; RNA Interference ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Short Stature Homeobox Protein ; Transcription, Genetic ; Wings, Animal/cytology ; Wings, Animal/embryology ; Wings, Animal/metabolism
Chemical Substances	Homeodomain Proteins ; Recombinant Proteins ; SHOX protein, human ; Short Stature Homeobox Protein ; Luciferases, Firefly (EC 1.13.12.7) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
Language	English
Publishing date	2011-04-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddr030
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Article: C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists.

Abin-Carriquiry, J Andrés / Voutilainen, Merja H / Barik, Jacques / Cassels, Bruce K / Iturriaga-Vásquez, Patricio / Bermudez, Isabel / Durand, Claudia / Dajas, Federico / Wonnacott, Susan

European journal of pharmacology

2006 Volume 536, Issue 1-2, Page(s) 1–11

Abstract: Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, ... ...

Abstract	Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, found in Leguminosae spp., binds with high affinity to alpha4beta2* nicotinic receptors. We have compared the effect of C3 and C5 halogenation of cytisine and methylcytisine (MCy) on their interaction with native rat nicotinic receptors. 3-Bromocytisine (3-BrCy) and 3-iodocytisine (3-ICy) exhibited increased binding affinity (especially at alpha7 nicotinic receptors; Ki approximately 0.1 microM) and functional potency, whereas C5-halogenation was detrimental. 3-BrCy and 3-ICy were more potent than cytisine at evoking [3H]dopamine release from striatal slices (EC50 approximately 11 nM), [3H]noradrenaline release from hippocampal slices (EC50 approximately 250 nM), increases in intracellular Ca2+ in PC12 cells and inward currents in Xenopus oocytes expressing human alpha3beta4 nicotinic receptor (EC50 approximately 2 microM). These compounds were also more efficacious than cytisine. C3-halogenation of cytisine is proposed to stabilize the open conformation of the nicotinic receptor but does not enhance subtype selectivity.
MeSH term(s)	Alkaloids/chemistry ; Alkaloids/metabolism ; Alkaloids/pharmacology ; Animals ; Azocines/chemistry ; Azocines/metabolism ; Azocines/pharmacology ; Binding, Competitive/drug effects ; Brain/drug effects ; Brain/metabolism ; Calcium/metabolism ; Dopamine/secretion ; Dose-Response Relationship, Drug ; Female ; Humans ; Hydrocarbons, Brominated/chemistry ; Hydrocarbons, Brominated/metabolism ; Hydrocarbons, Brominated/pharmacology ; Male ; Membrane Potentials/drug effects ; Nicotine/antagonists & inhibitors ; Nicotine/pharmacology ; Nicotinic Agonists/chemistry ; Nicotinic Agonists/metabolism ; Nicotinic Agonists/pharmacology ; Norepinephrine/secretion ; Oocytes/drug effects ; Oocytes/physiology ; PC12 Cells ; Quinolizines/chemistry ; Quinolizines/metabolism ; Quinolizines/pharmacology ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism ; Receptors, Nicotinic/physiology ; Xenopus
Chemical Substances	Alkaloids ; Azocines ; Hydrocarbons, Brominated ; Nicotinic Agonists ; Quinolizines ; Receptors, Nicotinic ; nicotinic receptor alpha3beta4 ; cytisine (53S5U404NU) ; Nicotine (6M3C89ZY6R) ; Calcium (SY7Q814VUP) ; Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2006-04-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2006.02.012
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