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Article ; Online: Possible role of human leukocyte antigen-G molecules in human oocyte/embryo secretome.

Rizzo, Roberta / Stignani, Marina / Melchiorri, Loredana / Baricordi, Olavio R

2009 Volume 70, Issue 12, Page(s) 970–975

Abstract: Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule observed for the first time in human cytotrophoblast. Several investigations have demonstrated the presence of soluble HLA-G in oocyte/embryo secretome. A focus on the possible role ...

Abstract	Human leucocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule observed for the first time in human cytotrophoblast. Several investigations have demonstrated the presence of soluble HLA-G in oocyte/embryo secretome. A focus on the possible role of HLA-G in oocyte/embryo context will be developed in this review. In addition, the possible use of HLA-G in assisted reproductive technology will be treated.
MeSH term(s)	Embryo, Mammalian/immunology ; Embryo, Mammalian/metabolism ; Female ; Follicular Fluid/immunology ; Follicular Fluid/metabolism ; HLA Antigens/immunology ; HLA Antigens/metabolism ; HLA-G Antigens ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Humans ; Maternal-Fetal Relations ; Oocytes/immunology ; Oocytes/metabolism ; Receptors, Immunologic/immunology ; Receptors, Immunologic/metabolism ; Receptors, KIR2DL5
Chemical Substances	HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Receptors, Immunologic ; Receptors, KIR2DL5
Language	English
Publishing date	2009-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2009.07.020
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Article ; Online: Comment on "Experimental extracorporeal photopheresis inhibits the sensitization and effector phases of contact hypersensitivity via two mechanisms: generation of IL-10 and induction of regulatory T cells".

Rizzo, Roberta / Stignani, Marina / Melchiorri, Loredana / Baricordi, Olavio R

Journal of immunology (Baltimore, Md. : 1950)

2009 Volume 182, Issue 8, Page(s) 4497

MeSH term(s)	Dermatitis, Contact/immunology ; Humans ; Interleukin-10/biosynthesis ; Interleukin-10/immunology ; Photopheresis ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Interleukin-10 (130068-27-8)
Language	English
Publishing date	2009-04-15
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.0990025
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Article: HLA-G and inflammatory diseases.

Baricordi, Olavio R / Stignani, Marina / Melchiorri, Loredana / Rizzo, Roberta

Inflammation & allergy drug targets

2008 Volume 7, Issue 2, Page(s) 67–74

Abstract: HLA-G antigens are non classical HLA-class I molecules characterized by a low allelic polymorphism, a limited tissue distribution and the presence of membrane bound and soluble isoforms. The HLA-G antigens were firstly detected in cytotrophoblast cells ... ...

Abstract	HLA-G antigens are non classical HLA-class I molecules characterized by a low allelic polymorphism, a limited tissue distribution and the presence of membrane bound and soluble isoforms. The HLA-G antigens were firstly detected in cytotrophoblast cells at the feto-maternal interface where they maintain a tolerogenic status between the mother and the semiallogenic fetus. Recently a variable expression of HLA-G molecules has been documented in several autoimmune diseases, viral infections, cancer diseases and transplantation. Overall the presence of HLA-G molecules in both membranes bound and soluble isoforms was associated with tolerogenic functions against innate and adaptative cellular responses. HLA-G antigens are able to affect the cytotoxicity of natural killer and CD8+ T cells, CD4+ T lymphocyte functions and dendritic cell maturation. In addition to the allelic polymorphism the HLA-G gene shows a deletion/insertion polymorphism of a 14 base pairs sequence (14bp) in the exon 8 at the 3' untranslated region. Several reports have associated the presence of the 14bp insertion allele (+14bp) to an unstable mRNA and a lower sHLA-G protein production, suggesting a different ability to counteract inflammation between genotypes. We reviewed the literature on the expression of HLA-G antigens in autoimmune and allergic diseases and the possible functional role of these molecules in counteracting inflammation.
MeSH term(s)	Alleles ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/metabolism ; Asthma/immunology ; Asthma/metabolism ; Central Nervous System/immunology ; Central Nervous System/metabolism ; Exons ; Gastrointestinal Diseases/immunology ; Gastrointestinal Diseases/metabolism ; HLA Antigens/blood ; HLA Antigens/genetics ; HLA Antigens/immunology ; HLA Antigens/metabolism ; HLA-G Antigens ; Histocompatibility Antigens Class I/blood ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Humans ; Immune Tolerance/immunology ; Inflammation/immunology ; Inflammation/metabolism ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/metabolism ; Protein Isoforms/immunology ; Protein Isoforms/metabolism ; RNA, Messenger/immunology ; RNA, Messenger/metabolism ; Skin/immunology ; Skin/metabolism ; Trophoblasts/immunology ; Trophoblasts/metabolism
Chemical Substances	HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Protein Isoforms ; RNA, Messenger
Language	English
Publishing date	2008-08-08
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2215862-5
ISSN	2212-4055 ; 1871-5281
ISSN (online)	2212-4055
ISSN	1871-5281
DOI	10.2174/187152808785107615
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Article: HLA-G expression is a fundamental prerequisite to pregnancy.

Rizzo, Roberta / Melchiorri, Loredana / Stignani, Marina / Baricordi, Olavio R

Human immunology

2007 Volume 68, Issue 4, Page(s) 244–250

Abstract: Human leukocyte antigen-G (HLA-G) is thought to play a key role in implantation by controlling trophoblast invasion and maintaining a local immunosuppressive state. The secretion of soluble HLA-G antigens (sHLA-G) by early embryos seems necessary for a ... ...

Abstract	Human leukocyte antigen-G (HLA-G) is thought to play a key role in implantation by controlling trophoblast invasion and maintaining a local immunosuppressive state. The secretion of soluble HLA-G antigens (sHLA-G) by early embryos seems necessary for a successful implantation and could be a marker of increased pregnancy rate following in vitro fertilization. We have reviewed the results obtained during the last years (from 1987 to 2005). They overall confirmed the predictive role of sHLA-G production in pregnancy outcome. Furthermore, we have examined the technical procedures utilized, with a particular attention to the monoclonal antibodies used in the enzyme-linked immunosorbent assay (ELISA) techniques. New functional roles for HLA-G molecules in pregnancy could be suggested by the relationship observed between the presence of sHLA-G antigens in follicular fluids and sHLA-G expression in the corresponding fertilized oocyte. Furthermore, since maternal mRNA is fundamental for protein production in early embryos, the biologic role of the HLA-G 14 base pair polymorphism could be explored.
MeSH term(s)	Female ; HLA Antigens/biosynthesis ; HLA Antigens/genetics ; HLA-G Antigens ; Histocompatibility Antigens Class I/biosynthesis ; Histocompatibility Antigens Class I/genetics ; Humans ; Pregnancy/immunology
Chemical Substances	HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I
Language	English
Publishing date	2007-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2006.10.012
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Article ; Online: Potential role of soluble human leukocyte antigen-G molecules in multiple sclerosis.

Fainardi, Enrico / Rizzo, Roberta / Castellazzi, Massimiliano / Stignani, Marina / Granieri, Enrico / Baricordi, Olavio Roberto

Human immunology

2009 Volume 70, Issue 12, Page(s) 981–987

Abstract: Nonclassical human leukocyte antigen (HLA)-G antigens in soluble form (sHLA-G) have recently been suggested to have a potential role as immunomodulatory factors in multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative ... ...

Abstract	Nonclassical human leukocyte antigen (HLA)-G antigens in soluble form (sHLA-G) have recently been suggested to have a potential role as immunomodulatory factors in multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system of unknown etiology and supposed autoimmune origin. In MS patients, sHLA-G levels were elevated in cerebrospinal fluid (CSF), intrathecally synthesized, predominantly represented by the HLA-G5 isoform and even more elevated in cases of inactive disease, as determined by magnetic resonance imaging. In MS, CSF sHLA-G concentrations were also related to the formation of an intrathecal anti-inflammatory microenvironment based on a positive correlation to CSF interleukin-10 titers and an inverse association to the levels of antiapoptotic sFas molecules in the CSF. Expression of HLA-G antigens was detected in microglia, macrophages, and endothelial cells within and around MS lesions and was enhanced in microglial cells by T-helper-1 proinflammatory cytokines. A novel subpopulation of naturally occurring CD4(+) and CD8(+) regulatory T cells expressing HLA-G1 and secreting HLA-G5 was identified in the CSF of MS patients. Taken together, these findings seem to indicate that sHLA-G antigens may be implicated in the termination of MS autoimmunity and associated with remission of the disease through their function as anti-inflammatory molecules. However, the mechanisms operating in the immunomodulatory circuit mediated by sHLA-G proteins remain to be clarified.
MeSH term(s)	Autoimmunity/immunology ; HLA Antigens/cerebrospinal fluid ; HLA Antigens/immunology ; HLA-G Antigens ; Histocompatibility Antigens Class I/cerebrospinal fluid ; Histocompatibility Antigens Class I/immunology ; Humans ; Interleukin-10/cerebrospinal fluid ; Multiple Sclerosis/immunology ; Multiple Sclerosis/physiopathology ; T-Lymphocyte Subsets/immunology ; fas Receptor/cerebrospinal fluid
Chemical Substances	HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; fas Receptor ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2009-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2009.07.014
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Article ; Online: Soluble human leukocyte antigen-g expression and glucose tolerance in subjects with different degrees of adiposity.

Solini, Anna / Muscelli, Elza / Stignani, Marina / Melchiorri, Loredana / Santini, Eleonora / Rossi, Chiara / Astiarraga, Brenno Domingues / Rizzo, Roberta / Baricordi, Olavio Roberto

The Journal of clinical endocrinology and metabolism

2010 Volume 95, Issue 7, Page(s) 3342–3346

Abstract: Context: Type 2 diabetes mellitus (T2DM) and obesity are characterized by a low-grade inflammation, which might be related to the development of insulin resistance. Human leukocyte antigen-G (HLA-G) shows antiinflammatory and tolerogenic properties, ... ...

Abstract	Context: Type 2 diabetes mellitus (T2DM) and obesity are characterized by a low-grade inflammation, which might be related to the development of insulin resistance. Human leukocyte antigen-G (HLA-G) shows antiinflammatory and tolerogenic properties, including the modulation of CD8+ T-cell cytotoxicity and regulation of CD4+ T-lymphocyte function. These functions are partially shared with IL-10, whose levels are reduced in insulin-resistant states. Objective: The aim was to explore the relationship between HLA-G and the metabolic and inflammatory pattern of obesity or T2DM. Patients and main outcome measures: Soluble HLA-G, IL-6, and IL-10 were measured and related with metabolic and biochemical parameters in 230 volunteers with normal glucose tolerance, impaired glucose tolerance, or T2DM by oral glucose tolerance test. Results: sHLA-G, detected in 144 subjects (sHLA-G positive), was more frequent in T2DM or impaired glucose tolerance subjects than in normal glucose tolerance (chi(2) =18.6; P < 0.0001), and its plasma levels increased progressively across the classes of glucose tolerance. sHLA-G-positive individuals had higher body mass index, systolic blood pressure, and cholesterol levels; a reduced degree of insulin sensitivity; and almost 2-fold higher levels of IL-6, a cytokine related to insulin sensitivity, whereas IL-10 was similar. In the sHLA-G-positive subgroup, by a multivariate regression model, sHLA-G was significantly related to 2-h glucose, the area under insulin curve, and IL-6 levels (multiple r(2) = 0.14; P < 0.001), independently of age, gender, and body mass index. Conclusions: A frequent expression of sHLA-G, linked to a typical biomarker of insulin resistance like IL-6, seems to characterize subjects with an impaired glucose metabolism.
MeSH term(s)	Adiposity/physiology ; Adult ; Analysis of Variance ; Biomarkers ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Glucose Intolerance/metabolism ; Glucose Intolerance/physiopathology ; Glucose Tolerance Test ; HLA Antigens/blood ; HLA-G Antigens ; Histocompatibility Antigens Class I/blood ; Humans ; Insulin/blood ; Interleukin-10/blood ; Interleukin-6/blood ; Male ; Middle Aged ; Obesity/metabolism ; Obesity/physiopathology ; Regression Analysis ; Statistics, Nonparametric
Chemical Substances	Biomarkers ; Blood Glucose ; HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Insulin ; Interleukin-6 ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2009-2747
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Article: Emerging topics and new perspectives on HLA-G

Fainardi, Enrico / Castellazzi, Massimiliano / Stignani, Marina / Morandi, Fabio / Sana, Gwenaëlle / Gonzalez, Rafael / Pistoia, Vito / Baricordi, Olavio Roberto / Sokal, Etienne / Peña, Josè

Cellular and molecular life sciences CMLS. 2011 Feb., v. 68, no. 3

2011

Abstract: Following the Fifth International Conference on non-classical HLA-G antigens (HLA-G), held in Paris in July 2009, we selected some topics which focus on emerging aspects in the setting of HLA-G functions. In particular, HLA-G molecules could play a role ... ...

Abstract	Following the Fifth International Conference on non-classical HLA-G antigens (HLA-G), held in Paris in July 2009, we selected some topics which focus on emerging aspects in the setting of HLA-G functions. In particular, HLA-G molecules could play a role in: (1) various inflammatory disorders, such as multiple sclerosis, intracerebral hemorrhage, gastrointestinal, skin and rheumatic diseases, and asthma, where they may act as immunoregulatory factors; (2) the mechanisms to escape immune surveillance utilized by several viruses, such as human cytomegalovirus, herpes simplex virus type 1, rabies virus, hepatitis C virus, influenza virus type A and human immunodeficiency virus 1 (HIV-1); and (3) cytokine/chemokine network and stem cell transplantation, since they seem to modulate cell migration by the downregulation of chemokine receptor expression and mesenchymal stem cell activity blocking of effector cell functions and the generation of regulatory T cells. However, the immunomodulatory circuits mediated by HLA-G proteins still remain to be clarified.
Keywords	inflammation ; stem cells
Language	English
Dates of publication	2011-02
Size	p. 433-451.
Publisher	SP Birkhäuser Verlag Basel
Publishing place	Basel
Document type	Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-010-0584-3
Database	NAL-Catalogue (AGRICOLA)

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Article: Polymorphism in the 5' upstream regulatory and 3' untranslated regions of the HLA-G gene in relation to soluble HLA-G and IL-10 expression.

Hviid, Thomas Vauvert F / Rizzo, Roberta / Melchiorri, Loredana / Stignani, Marina / Baricordi, Olavio R

Human immunology

2006 Volume 67, Issue 1-2, Page(s) 53–62

Abstract: The nonclassical human leukocyte antigen (HLA) class Ib gene HLA-G may be important for the induction and maintenance of immune tolerance between the mother and the semi-allogeneic fetus during pregnancy. Expression of HLA-G can influence cytokine and ... ...

Abstract	The nonclassical human leukocyte antigen (HLA) class Ib gene HLA-G may be important for the induction and maintenance of immune tolerance between the mother and the semi-allogeneic fetus during pregnancy. Expression of HLA-G can influence cytokine and cytotoxic T-lymphocyte responses. Different HLA-G mRNA isoform expression patterns have been associated with HLA-G polymorphism, especially with a 14-bp insertion deletion polymorphism in the 3' untranslated region (3'UTR) of the HLA-G gene. A significantly high level of interleukin-10 (IL-10) secretion is observed in homozygous +14/+14-bp HLA-G peripheral blood mononuclear cells after lipopolysaccharide (LPS) stimulation. This study finds that polymorphism in the 5' upstream regulatory region (5'URR) of the HLA-G gene may also be implicated in differences in IL-10 secretion. However, this may also be due to linkage disequilibrium with the 14-bp polymorphism. A single-nucleotide polymorphism located -477 bp from the start site of exon 1 had a significant association with IL-10 concentrations but not after correction (p=0.011; pc=0.154). This polymorphism is located next to a heat shock element. Eighteen 5'-URR/3'-UTR HLA-G haplotypes were defined; one common homozygous genotype based on these haplotypes was significantly associated with a high IL-10 level after LPS stimulation compared to certain other genotypes. This study indicates that polymorphism in the 5'-URR of the HLA-G gene may have functional significance, although a new line of investigations is needed to elucidate these findings.
MeSH term(s)	3' Untranslated Regions/genetics ; Base Sequence ; Gene Expression ; HLA Antigens/genetics ; HLA-G Antigens ; Histocompatibility Antigens Class I/genetics ; Humans ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Linkage Disequilibrium ; Lipopolysaccharides/pharmacology ; Molecular Sequence Data ; Polymorphism, Genetic ; Regulatory Elements, Transcriptional/genetics
Chemical Substances	3' Untranslated Regions ; HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Lipopolysaccharides ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2006-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2005.12.003
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Article: Reduced production of anti-inflammatory soluble HLA-G molecules in styrene exposed workers.

Rizzo, Roberta / Quintavalle, Sonia / Stignani, Marina / Franzè, Fabrizio / Melchiorri, Loredana / De Rosa, Edoardo / Baricordi, Olavio R

Environmental toxicology and pharmacology

2009 Volume 27, Issue 2, Page(s) 303–305

Abstract: HLA-G antigens are non-classical HLA-class I anti-inflammatory molecules. Since styrene exposure has been suggested to induce immune alteration, we analyzed plasma levels and "in vitro" peripheral blood mononuclear cell (PBMC) production of soluble HLA-G ...

Abstract	HLA-G antigens are non-classical HLA-class I anti-inflammatory molecules. Since styrene exposure has been suggested to induce immune alteration, we analyzed plasma levels and "in vitro" peripheral blood mononuclear cell (PBMC) production of soluble HLA-G (sHLA-G) and interleukin-10 (IL-10) molecules after lipopolysaccharide (LPS) stimulation, in styrene exposed workers and healthy subjects. Exposed workers showed reduced plasma levels of sHLA-G and IL-10 in comparison to healthy controls. Similarly, lower levels of sHLA-G and IL-10 molecules were observed in PBMC culture supernatants after LPS activation. These data propose styrene exposure as a mediator of impaired sHLA-G production.
Language	English
Publishing date	2009-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1382-6689
ISSN	1382-6689
DOI	10.1016/j.etap.2008.10.013
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Article ; Online: Allergic women have reduced sHLA-G plasma levels at delivery.

Rizzo, Roberta / Stignani, Marina / Amoudruz, Petra / Nilsson, Caroline / Melchiorri, Loredana / Baricordi, Olavio / Sverremark-Ekström, Eva

American journal of reproductive immunology (New York, N.Y. : 1989)

2009 Volume 61, Issue 5, Page(s) 368–376

Abstract: Problem: HLA-G antigen maintains a tolerogenic condition at the foeto-maternal interface, counteracts inflammation in autoimmune diseases and soluble HLA-G (sHLA-G) levels decrease in allergic-asthmatics. Taking into consideration these findings, we ... ...

Abstract	Problem: HLA-G antigen maintains a tolerogenic condition at the foeto-maternal interface, counteracts inflammation in autoimmune diseases and soluble HLA-G (sHLA-G) levels decrease in allergic-asthmatics. Taking into consideration these findings, we analyzed if sHLA-G and interleukin-10 (IL-10) could be influenced by pregnancy and labour in allergic and non-allergic women. Method of study: sHLA-G isoforms and IL-10 levels were determined in the plasma samples of 43 women (15 non-allergic, 28 allergic) during third trimester, at delivery and 2 years after pregnancy by immunoenzymatic assays. Results: A significant increase in sHLA-G and IL-10 levels was documented at delivery in both allergic and non-allergic women. Allergic women showed lower sHLA-G concentrations. sHLA-G1 was evidenced as the predominant plasma isoform. Conclusion: The data showed increased sHLA-G and IL-10 concentrations at delivery, regardless of the allergic status. The sHLA-G1 isoform is mainly responsible for the increased sHLA-G levels at delivery.
MeSH term(s)	Adult ; Female ; Follow-Up Studies ; HLA Antigens/blood ; HLA-G Antigens ; Histocompatibility Antigens Class I/blood ; Humans ; Hypersensitivity/blood ; Hypersensitivity/immunology ; Interleukin-10/blood ; Labor Onset/blood ; Labor Onset/immunology ; Pregnancy
Chemical Substances	HLA Antigens ; HLA-G Antigens ; Histocompatibility Antigens Class I ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2009-05
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604542-x
ISSN	1600-0897 ; 0271-7352 ; 8755-8920 ; 1046-7408
ISSN (online)	1600-0897
ISSN	0271-7352 ; 8755-8920 ; 1046-7408
DOI	10.1111/j.1600-0897.2009.00703.x
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