Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to...
Ausführliche Beschreibung
Autor*in: |
Feng Guo [verfasserIn] Yinyan Ma [verfasserIn] Anil K.G. Kadegowda [verfasserIn] Jenna L. Betters [verfasserIn] Ping Xie [verfasserIn] George Liu [verfasserIn] Xiuli Liu [verfasserIn] Hongming Miao [verfasserIn] Juanjuan Ou [verfasserIn] Xiong Su [verfasserIn] Zhenlin Zheng [verfasserIn] Bingzhong Xue [verfasserIn] Hang Shi [verfasserIn] Liqing Yu [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2013 |
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Übergeordnetes Werk: |
In: Journal of Lipid Research - Elsevier, 2021, 54(2013), 8, Seite 2109-2120 |
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Übergeordnetes Werk: |
volume:54 ; year:2013 ; number:8 ; pages:2109-2120 |
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DOI / URN: |
10.1194/jlr.M035519 |
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Katalog-ID: |
DOAJ057481598 |
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10.1194/jlr.M035519 doi (DE-627)DOAJ057481598 (DE-599)DOAJc612d0766f394fa39435d54e04dc42a4 DE-627 ger DE-627 rakwb eng QD415-436 Feng Guo verfasserin aut Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. triglyceride hydrolysis lipase fatty liver CGI-58 Biochemistry Yinyan Ma verfasserin aut Anil K.G. Kadegowda verfasserin aut Jenna L. Betters verfasserin aut Ping Xie verfasserin aut George Liu verfasserin aut Xiuli Liu verfasserin aut Hongming Miao verfasserin aut Juanjuan Ou verfasserin aut Xiong Su verfasserin aut Zhenlin Zheng verfasserin aut Bingzhong Xue verfasserin aut Hang Shi verfasserin aut Liqing Yu verfasserin aut In Journal of Lipid Research Elsevier, 2021 54(2013), 8, Seite 2109-2120 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:54 year:2013 number:8 pages:2109-2120 https://doi.org/10.1194/jlr.M035519 kostenfrei https://doaj.org/article/c612d0766f394fa39435d54e04dc42a4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520375271 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 54 2013 8 2109-2120 |
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10.1194/jlr.M035519 doi (DE-627)DOAJ057481598 (DE-599)DOAJc612d0766f394fa39435d54e04dc42a4 DE-627 ger DE-627 rakwb eng QD415-436 Feng Guo verfasserin aut Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. triglyceride hydrolysis lipase fatty liver CGI-58 Biochemistry Yinyan Ma verfasserin aut Anil K.G. Kadegowda verfasserin aut Jenna L. Betters verfasserin aut Ping Xie verfasserin aut George Liu verfasserin aut Xiuli Liu verfasserin aut Hongming Miao verfasserin aut Juanjuan Ou verfasserin aut Xiong Su verfasserin aut Zhenlin Zheng verfasserin aut Bingzhong Xue verfasserin aut Hang Shi verfasserin aut Liqing Yu verfasserin aut In Journal of Lipid Research Elsevier, 2021 54(2013), 8, Seite 2109-2120 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:54 year:2013 number:8 pages:2109-2120 https://doi.org/10.1194/jlr.M035519 kostenfrei https://doaj.org/article/c612d0766f394fa39435d54e04dc42a4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520375271 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 54 2013 8 2109-2120 |
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10.1194/jlr.M035519 doi (DE-627)DOAJ057481598 (DE-599)DOAJc612d0766f394fa39435d54e04dc42a4 DE-627 ger DE-627 rakwb eng QD415-436 Feng Guo verfasserin aut Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. triglyceride hydrolysis lipase fatty liver CGI-58 Biochemistry Yinyan Ma verfasserin aut Anil K.G. Kadegowda verfasserin aut Jenna L. Betters verfasserin aut Ping Xie verfasserin aut George Liu verfasserin aut Xiuli Liu verfasserin aut Hongming Miao verfasserin aut Juanjuan Ou verfasserin aut Xiong Su verfasserin aut Zhenlin Zheng verfasserin aut Bingzhong Xue verfasserin aut Hang Shi verfasserin aut Liqing Yu verfasserin aut In Journal of Lipid Research Elsevier, 2021 54(2013), 8, Seite 2109-2120 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:54 year:2013 number:8 pages:2109-2120 https://doi.org/10.1194/jlr.M035519 kostenfrei https://doaj.org/article/c612d0766f394fa39435d54e04dc42a4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520375271 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 54 2013 8 2109-2120 |
allfieldsGer |
10.1194/jlr.M035519 doi (DE-627)DOAJ057481598 (DE-599)DOAJc612d0766f394fa39435d54e04dc42a4 DE-627 ger DE-627 rakwb eng QD415-436 Feng Guo verfasserin aut Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. triglyceride hydrolysis lipase fatty liver CGI-58 Biochemistry Yinyan Ma verfasserin aut Anil K.G. Kadegowda verfasserin aut Jenna L. Betters verfasserin aut Ping Xie verfasserin aut George Liu verfasserin aut Xiuli Liu verfasserin aut Hongming Miao verfasserin aut Juanjuan Ou verfasserin aut Xiong Su verfasserin aut Zhenlin Zheng verfasserin aut Bingzhong Xue verfasserin aut Hang Shi verfasserin aut Liqing Yu verfasserin aut In Journal of Lipid Research Elsevier, 2021 54(2013), 8, Seite 2109-2120 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:54 year:2013 number:8 pages:2109-2120 https://doi.org/10.1194/jlr.M035519 kostenfrei https://doaj.org/article/c612d0766f394fa39435d54e04dc42a4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0022227520375271 kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 54 2013 8 2109-2120 |
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Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice |
abstract |
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. |
abstractGer |
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. |
abstract_unstemmed |
Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as α-smooth muscle actin, collagen type 1 α1, tumor necrosis factor α, and interleukin-1β. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis. |
collection_details |
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container_issue |
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title_short |
Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice |
url |
https://doi.org/10.1194/jlr.M035519 https://doaj.org/article/c612d0766f394fa39435d54e04dc42a4 http://www.sciencedirect.com/science/article/pii/S0022227520375271 https://doaj.org/toc/0022-2275 |
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author2 |
Yinyan Ma Anil K.G. Kadegowda Jenna L. Betters Ping Xie George Liu Xiuli Liu Hongming Miao Juanjuan Ou Xiong Su Zhenlin Zheng Bingzhong Xue Hang Shi Liqing Yu |
author2Str |
Yinyan Ma Anil K.G. Kadegowda Jenna L. Betters Ping Xie George Liu Xiuli Liu Hongming Miao Juanjuan Ou Xiong Su Zhenlin Zheng Bingzhong Xue Hang Shi Liqing Yu |
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doi_str |
10.1194/jlr.M035519 |
callnumber-a |
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up_date |
2024-07-04T01:50:15.290Z |
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