Monoacylglycerol signalling and ABHD6 in health and disease
Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic s...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2017-09, Vol.19 (S1), p.76-89 |
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| creator | Poursharifi, Pegah Madiraju, Sri Ramachandra Murthy Prentki, Marc |
| description | Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β‐hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2‐arachidonoylglycerol, which is a 2‐MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13‐1 (Munc13‐1), PPARs, GPR119 and CB1/2 receptors, for MAG‐mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications. |
| doi_str_mv | 10.1111/dom.13008 |
| format | Article |
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Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β‐hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2‐arachidonoylglycerol, which is a 2‐MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13‐1 (Munc13‐1), PPARs, GPR119 and CB1/2 receptors, for MAG‐mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.13008</identifier><identifier>PMID: 28880480</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>2‐AG ; ABHD6 ; adipose browning ; Animals ; Arachidonic Acids - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - enzymology ; Diabetes Mellitus, Type 2 - metabolism ; endocannabinoids ; Endocannabinoids - metabolism ; energy metabolism ; Energy Metabolism - drug effects ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Gene Expression Regulation, Enzymologic - drug effects ; Glycerides - metabolism ; Humans ; Insulin secretion ; Ligands ; lipid metabolism ; Lipids ; lipolysis ; metabolic syndrome ; Metabolic Syndrome - drug therapy ; Metabolic Syndrome - enzymology ; Metabolic Syndrome - metabolism ; Metabolism ; Models, Biological ; monoacylglycerol ; Monoacylglycerol Lipases - antagonists & inhibitors ; Monoacylglycerol Lipases - chemistry ; Monoacylglycerol Lipases - genetics ; Monoacylglycerol Lipases - metabolism ; Monoglycerides - metabolism ; Nerve Tissue Proteins - agonists ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Obesity - drug therapy ; Obesity - enzymology ; Obesity - metabolism ; Organ Specificity ; Peroxisome Proliferator-Activated Receptors - agonists ; Peroxisome Proliferator-Activated Receptors - genetics ; Peroxisome Proliferator-Activated Receptors - metabolism ; Receptors, G-Protein-Coupled - agonists ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Second Messenger Systems - drug effects ; Substrate Specificity ; TRPV Cation Channels - agonists ; TRPV Cation Channels - genetics ; TRPV Cation Channels - metabolism ; α/β Hydrolase domain containing 6</subject><ispartof>Diabetes, obesity & metabolism, 2017-09, Vol.19 (S1), p.76-89</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3888-4490ad276052beeedea96791770b10337dc9833bc0eb8c1db809f62909603af93</citedby><cites>FETCH-LOGICAL-c3888-4490ad276052beeedea96791770b10337dc9833bc0eb8c1db809f62909603af93</cites><orcidid>0000-0002-2613-2074</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.13008$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.13008$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28880480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poursharifi, Pegah</creatorcontrib><creatorcontrib>Madiraju, Sri Ramachandra Murthy</creatorcontrib><creatorcontrib>Prentki, Marc</creatorcontrib><title>Monoacylglycerol signalling and ABHD6 in health and disease</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β‐hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2‐arachidonoylglycerol, which is a 2‐MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13‐1 (Munc13‐1), PPARs, GPR119 and CB1/2 receptors, for MAG‐mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications.</description><subject>2‐AG</subject><subject>ABHD6</subject><subject>adipose browning</subject><subject>Animals</subject><subject>Arachidonic Acids - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - enzymology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>endocannabinoids</subject><subject>Endocannabinoids - metabolism</subject><subject>energy metabolism</subject><subject>Energy Metabolism - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Glycerides - metabolism</subject><subject>Humans</subject><subject>Insulin secretion</subject><subject>Ligands</subject><subject>lipid metabolism</subject><subject>Lipids</subject><subject>lipolysis</subject><subject>metabolic syndrome</subject><subject>Metabolic Syndrome - drug therapy</subject><subject>Metabolic Syndrome - enzymology</subject><subject>Metabolic Syndrome - metabolism</subject><subject>Metabolism</subject><subject>Models, Biological</subject><subject>monoacylglycerol</subject><subject>Monoacylglycerol Lipases - antagonists & inhibitors</subject><subject>Monoacylglycerol Lipases - chemistry</subject><subject>Monoacylglycerol Lipases - genetics</subject><subject>Monoacylglycerol Lipases - metabolism</subject><subject>Monoglycerides - metabolism</subject><subject>Nerve Tissue Proteins - agonists</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Obesity - drug therapy</subject><subject>Obesity - enzymology</subject><subject>Obesity - metabolism</subject><subject>Organ Specificity</subject><subject>Peroxisome Proliferator-Activated Receptors - agonists</subject><subject>Peroxisome Proliferator-Activated Receptors - genetics</subject><subject>Peroxisome Proliferator-Activated Receptors - metabolism</subject><subject>Receptors, G-Protein-Coupled - agonists</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Second Messenger Systems - drug effects</subject><subject>Substrate Specificity</subject><subject>TRPV Cation Channels - agonists</subject><subject>TRPV Cation Channels - genetics</subject><subject>TRPV Cation Channels - metabolism</subject><subject>α/β Hydrolase domain containing 6</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLFOwzAQhi0EoqUw8AIoEgsMac92cGwxlRYoUqsuMFtO7LSpnLjEjVDenrQpDEjccqfTp-90P0LXGIa4rZF2xRBTAH6C-jhiNMSUsNPDTEIugPTQhfcbAIgoj89Rj3DOIeLQR48LVzqVNnZlm9RUzgY-X5XK2rxcBarUwfhpNmVBXgZro-xufdjp3BvlzSU6y5T15urYB-jj5fl9Mgvny9e3yXgeprS9E0aRAKVJzOCBJMYYbZRgscBxDAkGSmOdCk5pkoJJeIp1wkFkjAgQDKjKBB2gu867rdxnbfxOFrlPjbWqNK72EgvKGKEEsxa9_YNuXF21_3QUwTTme-F9R6WV874ymdxWeaGqRmKQ-0Rlm6g8JNqyN0djnRRG_5I_EbbAqAO-cmua_01yulx0ym-NiHyk</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Poursharifi, Pegah</creator><creator>Madiraju, Sri Ramachandra Murthy</creator><creator>Prentki, Marc</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2613-2074</orcidid></search><sort><creationdate>201709</creationdate><title>Monoacylglycerol signalling and ABHD6 in health and disease</title><author>Poursharifi, Pegah ; Madiraju, Sri Ramachandra Murthy ; Prentki, Marc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3888-4490ad276052beeedea96791770b10337dc9833bc0eb8c1db809f62909603af93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>2‐AG</topic><topic>ABHD6</topic><topic>adipose browning</topic><topic>Animals</topic><topic>Arachidonic Acids - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - enzymology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>endocannabinoids</topic><topic>Endocannabinoids - metabolism</topic><topic>energy metabolism</topic><topic>Energy Metabolism - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Glycerides - metabolism</topic><topic>Humans</topic><topic>Insulin secretion</topic><topic>Ligands</topic><topic>lipid metabolism</topic><topic>Lipids</topic><topic>lipolysis</topic><topic>metabolic syndrome</topic><topic>Metabolic Syndrome - drug therapy</topic><topic>Metabolic Syndrome - enzymology</topic><topic>Metabolic Syndrome - metabolism</topic><topic>Metabolism</topic><topic>Models, Biological</topic><topic>monoacylglycerol</topic><topic>Monoacylglycerol Lipases - antagonists & inhibitors</topic><topic>Monoacylglycerol Lipases - chemistry</topic><topic>Monoacylglycerol Lipases - genetics</topic><topic>Monoacylglycerol Lipases - metabolism</topic><topic>Monoglycerides - metabolism</topic><topic>Nerve Tissue Proteins - agonists</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Obesity - drug therapy</topic><topic>Obesity - enzymology</topic><topic>Obesity - metabolism</topic><topic>Organ Specificity</topic><topic>Peroxisome Proliferator-Activated Receptors - agonists</topic><topic>Peroxisome Proliferator-Activated Receptors - genetics</topic><topic>Peroxisome Proliferator-Activated Receptors - metabolism</topic><topic>Receptors, G-Protein-Coupled - agonists</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Second Messenger Systems - drug effects</topic><topic>Substrate Specificity</topic><topic>TRPV Cation Channels - agonists</topic><topic>TRPV Cation Channels - genetics</topic><topic>TRPV Cation Channels - metabolism</topic><topic>α/β Hydrolase domain containing 6</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Poursharifi, Pegah</creatorcontrib><creatorcontrib>Madiraju, Sri Ramachandra Murthy</creatorcontrib><creatorcontrib>Prentki, Marc</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poursharifi, Pegah</au><au>Madiraju, Sri Ramachandra Murthy</au><au>Prentki, Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monoacylglycerol signalling and ABHD6 in health and disease</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2017-09</date><risdate>2017</risdate><volume>19</volume><issue>S1</issue><spage>76</spage><epage>89</epage><pages>76-89</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β‐hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2‐arachidonoylglycerol, which is a 2‐MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13‐1 (Munc13‐1), PPARs, GPR119 and CB1/2 receptors, for MAG‐mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>28880480</pmid><doi>10.1111/dom.13008</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-2613-2074</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 2‐AG ABHD6 adipose browning Animals Arachidonic Acids - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - enzymology Diabetes Mellitus, Type 2 - metabolism endocannabinoids Endocannabinoids - metabolism energy metabolism Energy Metabolism - drug effects Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Gene Expression Regulation, Enzymologic - drug effects Glycerides - metabolism Humans Insulin secretion Ligands lipid metabolism Lipids lipolysis metabolic syndrome Metabolic Syndrome - drug therapy Metabolic Syndrome - enzymology Metabolic Syndrome - metabolism Metabolism Models, Biological monoacylglycerol Monoacylglycerol Lipases - antagonists & inhibitors Monoacylglycerol Lipases - chemistry Monoacylglycerol Lipases - genetics Monoacylglycerol Lipases - metabolism Monoglycerides - metabolism Nerve Tissue Proteins - agonists Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Obesity - drug therapy Obesity - enzymology Obesity - metabolism Organ Specificity Peroxisome Proliferator-Activated Receptors - agonists Peroxisome Proliferator-Activated Receptors - genetics Peroxisome Proliferator-Activated Receptors - metabolism Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Second Messenger Systems - drug effects Substrate Specificity TRPV Cation Channels - agonists TRPV Cation Channels - genetics TRPV Cation Channels - metabolism α/β Hydrolase domain containing 6 |
| title | Monoacylglycerol signalling and ABHD6 in health and disease |
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