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  1. Article ; Online: Homeostatic plasticity and burst activity are mediated by hyperpolarization-activated cation currents and T-type calcium channels in neuronal cultures.

    Rátkai, Anikó / Tárnok, Krisztián / Aouad, Hajar El / Micska, Brigitta / Schlett, Katalin / Szücs, Attila

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3236

    Abstract: Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. We investigated the homeostatic regulation of hyperpolarization-activated cyclic ... ...

    Abstract Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. We investigated the homeostatic regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) and T-type calcium (Ca
    MeSH term(s) Action Potentials ; Animals ; Calcium Channels, T-Type/metabolism ; Cell Culture Techniques ; Cells, Cultured ; Hippocampus/cytology ; Hippocampus/metabolism ; Mice ; Neurons/cytology ; Neurons/metabolism
    Chemical Substances Cacna1g protein, mouse ; Cacna1h protein, mouse ; Cacna1i protein, mouse ; Calcium Channels, T-Type
    Language English
    Publishing date 2021-02-05
    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/s41598-021-82775-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Phase separation by ssDNA binding protein controlled via protein-protein and protein-DNA interactions.

    Harami, Gábor M / Kovács, Zoltán J / Pancsa, Rita / Pálinkás, János / Baráth, Veronika / Tárnok, Krisztián / Málnási-Csizmadia, András / Kovács, Mihály

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

    2020  Volume 117, Issue 42, Page(s) 26206–26217

    Abstract: Bacterial single-stranded (ss)DNA-binding proteins (SSB) are essential for the replication and maintenance of the genome. SSBs share a conserved ssDNA-binding domain, a less conserved intrinsically disordered linker (IDL), and a highly conserved C- ... ...

    Abstract Bacterial single-stranded (ss)DNA-binding proteins (SSB) are essential for the replication and maintenance of the genome. SSBs share a conserved ssDNA-binding domain, a less conserved intrinsically disordered linker (IDL), and a highly conserved C-terminal peptide (CTP) motif that mediates a wide array of protein-protein interactions with DNA-metabolizing proteins. Here we show that the
    MeSH term(s) DNA Damage ; DNA Repair ; DNA Repair Enzymes/genetics ; DNA Repair Enzymes/metabolism ; DNA, Single-Stranded/genetics ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/isolation & purification ; DNA-Binding Proteins/metabolism ; Escherichia coli/genetics ; Escherichia coli/growth & development ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/isolation & purification ; Escherichia coli Proteins/metabolism ; Liquid-Liquid Extraction/methods ; Protein Binding
    Chemical Substances DNA, Single-Stranded ; DNA-Binding Proteins ; Escherichia coli Proteins ; DNA Repair Enzymes (EC 6.5.1.-)
    Language English
    Publishing date 2020-10-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2000761117
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  3. Article ; Online: Protein kinase D exerts neuroprotective functions during oxidative stress via nuclear factor kappa B-independent signaling pathways.

    Liliom, Hanna / Tárnok, Krisztián / Ábrahám, Zsófia / Rácz, Bence / Hausser, Angelika / Schlett, Katalin

    Journal of neurochemistry

    2017  Volume 142, Issue 6, Page(s) 948–961

    Abstract: Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here, we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by ... ...

    Abstract Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here, we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by H
    Language English
    Publishing date 2017-08-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.14131
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  4. Article ; Online: A new tool for the quantitative analysis of dendritic filopodial motility.

    Tárnok, Krisztián / Gulyás, Márton / Bencsik, Norbert / Ferenc, Katalin / Pfizenmaier, Klaus / Hausser, Angelika / Schlett, Katalin

    Cytometry. Part A : the journal of the International Society for Analytical Cytology

    2015  Volume 87, Issue 1, Page(s) 89–96

    Abstract: Dendritic filopodia are tiny and highly motile protrusions formed along the dendrites of neurons. During the search for future presynaptic partners, their shape and size change dynamically, with a direct impact on the formation, stabilization and ... ...

    Abstract Dendritic filopodia are tiny and highly motile protrusions formed along the dendrites of neurons. During the search for future presynaptic partners, their shape and size change dynamically, with a direct impact on the formation, stabilization and maintenance of synaptic connections both in vivo and in vitro. In order to reveal molecular players regulating synapse formation, quantitative analysis of dendritic filopodia motility is needed. Defining the length or the tips of these protrusions manually, however, is time consuming, limiting the extent of studies as well as their statistical power. Additionally, area detection based on defining a single intensity threshold can lead to significant errors throughout the image series, as these small structures often have low contrast in fluorescent images. To overcome these problems, the open access Dendritic Filopodia Motility Analyzer, a semi-automated ImageJ/Fiji plugin was created. Our method calculates the displacement of the centre of mass (CoM) within a selected region based on the weighted intensity values of structure forming pixels, selected by upper and lower intensity thresholds. Using synthetic and real biological samples, we prove that the displacement of the weighted CoM reliably characterizes the motility of dendritic protrusions. Additionally, guidelines to define optimal parameters of live cell recordings from dendritic protrusions are provided. © 2014 International Society for Advancement of Cytometry.
    MeSH term(s) Animals ; Cell Movement ; Cytophotometry/instrumentation ; Cytophotometry/methods ; Dendrites/metabolism ; Dendrites/ultrastructure ; Embryo, Mammalian ; Gene Expression ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Hippocampus/metabolism ; Hippocampus/ultrastructure ; Image Processing, Computer-Assisted ; Mice ; Primary Cell Culture ; Pseudopodia/metabolism ; Pseudopodia/ultrastructure ; Synapses/metabolism ; Synapses/ultrastructure ; Time-Lapse Imaging/instrumentation ; Time-Lapse Imaging/methods
    Chemical Substances enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2015-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099868-5
    ISSN 1552-4930 ; 0196-4763 ; 1552-4922
    ISSN (online) 1552-4930
    ISSN 0196-4763 ; 1552-4922
    DOI 10.1002/cyto.a.22569
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  5. Article ; Online: The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans.

    Farkas, Zsolt / Fancsalszky, Luca / Saskői, Éva / Gráf, Alexandra / Tárnok, Krisztián / Mehta, Anil / Takács-Vellai, Krisztina

    Laboratory investigation; a journal of technical methods and pathology

    2017  Volume 98, Issue 2, Page(s) 182–189

    Abstract: Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is ... ...

    Abstract Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23. In human cancer cell lines NM23-H1 was shown to regulate cytoskeleton dynamics through inactivation of Rho/Rac-type GTPases. The Drosophila melanogaster NM23 homolog abnormal wing disc (AWD) controls tracheal and border cell migration. The molecular function of AWD is well characterized in both processes as a GTP supplier of Shi/Dynamin whereby AWD regulates the level of chemotactic receptors on the surface of migrating cells through receptor internalization, by its endocytic function. Our group studied the role of the sole group I NDPK, NDK-1 in distal tip cell (DTC) migration in Caenorhabditis elegans. In the absence of NDK-1 the migration of DTCs is incomplete. A half dosage of NDPK as present in ndk-1 (+/-) heterozygotes results in extra turns and overshoots of migrating gonad arms. Conversely, an elevated NDPK level also leads to incomplete gonadal migration owing to a premature stop of DTCs in the third phase of migration, where NDK-1 acts. We propose that NDK-1 exerts a dosage-dependent effect on the migration of DTCs. Our data derived from DTC migration in C. elegans is consistent with data on AWD's function in Drosophila. The combined data suggest that NDPK enzymes control the availability of surface receptors to regulate cell-sensing cues during cell migration. The dosage of NDPKs may be a coupling factor in cell migration by modulating the efficiency of receptor recycling.
    MeSH term(s) Animals ; Caenorhabditis elegans/enzymology ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Movement/genetics ; Heterozygote ; Humans ; Mutation ; NM23 Nucleoside Diphosphate Kinases/genetics ; NM23 Nucleoside Diphosphate Kinases/metabolism ; Signal Transduction/genetics
    Chemical Substances Caenorhabditis elegans Proteins ; NM23 Nucleoside Diphosphate Kinases
    Language English
    Publishing date 2017-09-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1038/labinvest.2017.99
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  6. Article: Anoxia leads to a rapid translocation of human trypsinogen 4 to the plasma membrane of cultured astrocytes

    Tárnok, Krisztián / Szilágyi, László / Berki, Tímea / Németh, Péter / Gráf, László / Schlett, Katalin

    Journal of neurochemistry. 2010 Oct., v. 115, no. 2

    2010  

    Abstract: J. Neurochem. (2010) 115, 314-324. Trypsinogen 4 is specifically expressed in the human brain, mainly by astroglial cells. Although its exact role in the nervous tissue is yet unclear, trypsin 4-mediated pathological processes were suggested in Alzheimer' ...

    Abstract J. Neurochem. (2010) 115, 314-324. Trypsinogen 4 is specifically expressed in the human brain, mainly by astroglial cells. Although its exact role in the nervous tissue is yet unclear, trypsin 4-mediated pathological processes were suggested in Alzheimer's disease, multiple sclerosis and ischemic injury. In the present study, we analyzed the intracellular distribution of fluorescently tagged human trypsinogen 4 isoforms during normal and anoxic conditions in transfected mouse primary astrocytes. Our results show that initiation of anoxic milieu by the combined action of KCN treatment and glucose deprivation rapidly leads to the association of leader peptide containing trypsinogen 4 constructs to the plasma membrane. Using rhodamine 110 bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide), a synthetic chromogen peptide substrate of trypsin, we show that anoxia can promote extracellular activation of trypsinogen 4 indicating that extracellular activation of human trypsinogen 4 can be an important component in neuropathological changes of the injured human brain.
    Keywords hypoxia ; astrocytes
    Language English
    Dates of publication 2010-10
    Size p. 314-324.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2010.06685.x
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  7. Article ; Online: NMDA receptor NR2B subunit over-expression increases cerebellar granule cell migratory activity.

    Tárnok, Krisztián / Czöndör, Katalin / Jelitai, Márta / Czirók, András / Schlett, Katalin

    Journal of neurochemistry

    2008  Volume 104, Issue 3, Page(s) 818–829

    Abstract: Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during ... ...

    Abstract Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during migration towards the internal granule cell layer but are gradually replaced by NR2A and/or NR2C subunits once the final position is reached. Cerebellar granule cell migration was investigated using mutant mouse lines either with a deletion of the NR2C gene (NR2C(-/-) mice) or expressing NR2B instead of the NR2C subunit (NR2C-2B mice). BrdU-labeling revealed that over-expression of NR2B increased granule cell translocation in vivo, while the lack of NR2C subunit did not have any detectable effects on cell migration. Cellular composition of wild-type and mutant dissociated cerebellar granule cell cultures isolated from 10-day-old cerebella were similar, but NR2C-2B cultures had elevated level of NR2B subunits and intracellular Ca2+ imaging revealed higher sensitivity towards the addition of NR2B-selective antagonist in vitro. Time-lapse videomicroscopic observations revealed that average migratory velocity and the proportion of translocating cell bodies were significantly higher in NR2C-2B than in wild-type cultures. Our results provide evidence that NR2B-containing NMDARs can have specialized roles during granule cell migration and can increase migratory speed.
    MeSH term(s) Animals ; Animals, Newborn ; Bromodeoxyuridine/metabolism ; Calcium/metabolism ; Cell Movement/drug effects ; Cell Movement/physiology ; Cells, Cultured ; Cerebellum/cytology ; Dizocilpine Maleate/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Gene Expression Regulation/physiology ; Growth Cones/drug effects ; Growth Cones/physiology ; Mice ; Mice, Knockout ; Microscopy, Video/methods ; Mutation/physiology ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Receptors, N-Methyl-D-Aspartate/deficiency ; Receptors, N-Methyl-D-Aspartate/metabolism
    Chemical Substances Excitatory Amino Acid Antagonists ; NR2B NMDA receptor ; NR2C NMDA receptor ; Receptors, N-Methyl-D-Aspartate ; Dizocilpine Maleate (6LR8C1B66Q) ; Bromodeoxyuridine (G34N38R2N1) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2008-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2007.05051.x
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  8. Article: Cerebellar granule cells show age-dependent migratory differences in vitro.

    Tárnok, Krisztián / Czirók, András / Czöndör, Katalin / Schlett, Katalin

    Journal of neurobiology

    2005  Volume 65, Issue 2, Page(s) 135–145

    Abstract: Developmental differences between cerebellar granule cells during their migratory period were revealed using dissociated granule cell cultures isolated from 4, 7, or 10 days old (P4, P7, P10) mice. Under all culture conditions, the great majority of ... ...

    Abstract Developmental differences between cerebellar granule cells during their migratory period were revealed using dissociated granule cell cultures isolated from 4, 7, or 10 days old (P4, P7, P10) mice. Under all culture conditions, the great majority of cultivated cell populations consisted of those granule cells that had not reach their final destination in the internal granule cell layer (IGL) by the age of isolation. In vitro morphological development and the expression of migratory markers (TAG-1, astrotactin, or EphB2) showed similar characteristics between the cultures. The migration of 1008 granule cells isolated from P4, P7, and P10 cerebella and cultivated under identical conditions were analyzed using statistical methods. In vitro time-lapse videomicroscopy revealed that P4 cells possessed the fastest migratory speed while P10 granule cells retained their migratory activity for the longest time in culture. Cultures obtained from younger postnatal ages showed more random migratory trajectories than P10 cultures. Our observations indicate that despite similar morphological and molecular properties, migratory differences exist in granule cell cultures isolated from different postnatal ages. Therefore, the age of investigation can substantially influence experimental results on the regulation of cell migration.
    MeSH term(s) Age Factors ; Animals ; Animals, Newborn ; Cell Movement/physiology ; Cells, Cultured ; Cerebellum/cytology ; Cerebellum/growth & development ; In Vitro Techniques ; Mice ; Mice, Inbred C57BL ; Neurites/physiology ; Neurons/physiology ; Neurons/ultrastructure
    Language English
    Publishing date 2005-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 300903-8
    ISSN 1097-4695 ; 0022-3034
    ISSN (online) 1097-4695
    ISSN 0022-3034
    DOI 10.1002/neu.20173
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  9. Article ; Online: Anoxia leads to a rapid translocation of human trypsinogen 4 to the plasma membrane of cultured astrocytes.

    Tárnok, Krisztián / Szilágyi, László / Berki, Tímea / Németh, Péter / Gráf, László / Schlett, Katalin

    Journal of neurochemistry

    2010  Volume 115, Issue 2, Page(s) 314–324

    Abstract: Trypsinogen 4 is specifically expressed in the human brain, mainly by astroglial cells. Although its exact role in the nervous tissue is yet unclear, trypsin 4-mediated pathological processes were suggested in Alzheimer's disease, multiple sclerosis and ... ...

    Abstract Trypsinogen 4 is specifically expressed in the human brain, mainly by astroglial cells. Although its exact role in the nervous tissue is yet unclear, trypsin 4-mediated pathological processes were suggested in Alzheimer's disease, multiple sclerosis and ischemic injury. In the present study, we analyzed the intracellular distribution of fluorescently tagged human trypsinogen 4 isoforms during normal and anoxic conditions in transfected mouse primary astrocytes. Our results show that initiation of anoxic milieu by the combined action of KCN treatment and glucose deprivation rapidly leads to the association of leader peptide containing trypsinogen 4 constructs to the plasma membrane. Using rhodamine 110 bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide), a synthetic chromogen peptide substrate of trypsin, we show that anoxia can promote extracellular activation of trypsinogen 4 indicating that extracellular activation of human trypsinogen 4 can be an important component in neuropathological changes of the injured human brain.
    MeSH term(s) Animals ; Animals, Newborn ; Astrocytes/drug effects ; Astrocytes/ultrastructure ; Cell Hypoxia/physiology ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cells, Cultured ; Cerebral Cortex/cytology ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Green Fluorescent Proteins/genetics ; Humans ; Mice ; Protein Isoforms/metabolism ; Protein Transport/drug effects ; Scanning Laser Polarimetry/methods ; Transfection/methods ; Trypsin/genetics ; Trypsin/metabolism ; Trypsin/pharmacology
    Chemical Substances Enzyme Inhibitors ; Protein Isoforms ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; PRSS3 protein, human (EC 3.4.21.4) ; Trypsin (EC 3.4.21.4)
    Language English
    Publishing date 2010-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2010.06685.x
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  10. Article: NMDA receptor NR2B subunit over-expression increases cerebellar granule cell migratory activity

    Tárnok, Krisztián / Czöndör, Katalin / Jelitai, Márta / Czirók, András / Schlett, Katalin

    Journal of neurochemistry. 2008 Feb., v. 104, no. 3

    2008  

    Abstract: Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during ... ...

    Abstract Glutamate acting on NMDA receptors (NMDARs) is known to influence cerebellar granule cell migration. Subunit composition of NMDARs in granule cells changes characteristically during development: NR2B subunit containing receptors are abundant during migration towards the internal granule cell layer but are gradually replaced by NR2A and/or NR2C subunits once the final position is reached. Cerebellar granule cell migration was investigated using mutant mouse lines either with a deletion of the NR2C gene (NR2C⁻/⁻ mice) or expressing NR2B instead of the NR2C subunit (NR2C-2B mice). BrdU-labeling revealed that over-expression of NR2B increased granule cell translocation in vivo, while the lack of NR2C subunit did not have any detectable effects on cell migration. Cellular composition of wild-type and mutant dissociated cerebellar granule cell cultures isolated from 10-day-old cerebella were similar, but NR2C-2B cultures had elevated level of NR2B subunits and intracellular Ca²⁺ imaging revealed higher sensitivity towards the addition of NR2B-selective antagonist in vitro. Time-lapse videomicroscopic observations revealed that average migratory velocity and the proportion of translocating cell bodies were significantly higher in NR2C-2B than in wild-type cultures. Our results provide evidence that NR2B-containing NMDARs can have specialized roles during granule cell migration and can increase migratory speed.
    Keywords cerebellum
    Language English
    Dates of publication 2008-02
    Size p. 818-829.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/j.1471-4159.2007.05051.x
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