Fawzia Bardag-Gorce

Summary

Affiliation: Los Angeles Biomedical Research Institute
Country: USA

Publications

  1. doi request reprint Independent phenotype of binuclear hepatocytes and cellular localization of UbD
    Joan Oliva
    Department of Pathology, LABiomed, Torrance, CA 90502, USA
    Exp Mol Pathol 89:103-8. 2010
  2. pmc Nuclear effects of ethanol-induced proteasome inhibition in liver cells
    Fawzia Bardag-Gorce
    The Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 W Carson St Torrance, CA 90502, United States
    World J Gastroenterol 15:1163-7. 2009
  3. pmc SAMe prevents the induction of the immunoproteasome and preserves the 26S proteasome in the DDC-induced MDB mouse model
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 88:353-62. 2010
  4. pmc Effects of ethanol on the proteasome interacting proteins
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, 1124 W Carson St, Los Angeles, CA 90509, USA
    World J Gastroenterol 16:1349-57. 2010
  5. pmc Proteasome inhibitor up regulates liver antioxidative enzymes in rat model of alcoholic liver disease
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 90:123-30. 2011
  6. pmc Proteasome inhibitor treatment in alcoholic liver disease
    Fawzia Bardag-Gorce
    Department of Pathology, Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, 1124 W Carson St, Torrance, CA 90502, United States
    World J Gastroenterol 17:2558-62. 2011
  7. pmc Epigenetic mechanisms regulate Mallory Denk body formation in the livers of drug-primed mice
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 84:113-21. 2008
  8. pmc The role of cytokines in UbD promoter regulation and Mallory-Denk body-like aggresomes
    Joan Oliva
    Department of Pathology, LABiomed, Torrance, CA 90502, USA
    Exp Mol Pathol 89:1-8. 2010
  9. pmc Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street Torrance, CA 90509, USA
    Exp Mol Pathol 84:102-12. 2008
  10. ncbi request reprint CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 81:191-201. 2006

Collaborators

Detail Information

Publications49

  1. doi request reprint Independent phenotype of binuclear hepatocytes and cellular localization of UbD
    Joan Oliva
    Department of Pathology, LABiomed, Torrance, CA 90502, USA
    Exp Mol Pathol 89:103-8. 2010
    ..The identification of proteins that interact with UbD and the post translational modification of UbD would help to determine the regulation of this localization and function...
  2. pmc Nuclear effects of ethanol-induced proteasome inhibition in liver cells
    Fawzia Bardag-Gorce
    The Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 W Carson St Torrance, CA 90502, United States
    World J Gastroenterol 15:1163-7. 2009
    ..The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol...
  3. pmc SAMe prevents the induction of the immunoproteasome and preserves the 26S proteasome in the DDC-induced MDB mouse model
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 88:353-62. 2010
    ..These results support the conclusion that MDBs form in FAT10 over-expressing hepatocytes where the up regulation of the immunoproteasome occurs at the expense of the 26S proteasome...
  4. pmc Effects of ethanol on the proteasome interacting proteins
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, 1124 W Carson St, Los Angeles, CA 90509, USA
    World J Gastroenterol 16:1349-57. 2010
    ....
  5. pmc Proteasome inhibitor up regulates liver antioxidative enzymes in rat model of alcoholic liver disease
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 90:123-30. 2011
    ..In conclusion, proteasome inhibitor treatment used at a non toxic low dose has potential protective effects against oxidative stress due to chronic ethanol feeding...
  6. pmc Proteasome inhibitor treatment in alcoholic liver disease
    Fawzia Bardag-Gorce
    Department of Pathology, Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, 1124 W Carson St, Torrance, CA 90502, United States
    World J Gastroenterol 17:2558-62. 2011
    ..The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration...
  7. pmc Epigenetic mechanisms regulate Mallory Denk body formation in the livers of drug-primed mice
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 84:113-21. 2008
    ..The results indicate that SAMe prevented the epigenetic cellular memory involved in the MDB formation...
  8. pmc The role of cytokines in UbD promoter regulation and Mallory-Denk body-like aggresomes
    Joan Oliva
    Department of Pathology, LABiomed, Torrance, CA 90502, USA
    Exp Mol Pathol 89:1-8. 2010
    ..Previous studies indicate that S-adenosylmethionine or betaine prevented IFNg induced UbD and MDB formations...
  9. pmc Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street Torrance, CA 90509, USA
    Exp Mol Pathol 84:102-12. 2008
    ..The refeeding of DDC increased the percent of FAT10 hepatocytes...
  10. ncbi request reprint CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed at Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 81:191-201. 2006
    ..This is the first report where ethanol caused Mallory body-like cytokeratin inclusions in transformed human liver cells in vitro...
  11. ncbi request reprint Mallory body (cytokeratin aggresomes) formation is prevented in vitro by p38 inhibitor
    Li Nan
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 80:228-40. 2006
    ..The data supported the concept that MBs form as the result of hyperphosphorylation of cytokeratin 8 by p38...
  12. ncbi request reprint CYP2E1 inhibition enhances mallory body formation
    Fawzia Bardag-Gorce
    Harbor UCLA Medical Center, L A Biomed, 1000 W Carson Street, Torrance, CA 90502, USA
    Exp Mol Pathol 78:207-11. 2005
    ..It was concluded that CYP2E1 inhibits MB formation by increasing the rate of elimination of DDC and/or its toxic intermediates...
  13. ncbi request reprint RNA interference of VCP/p97 increases Mallory body formation
    Li Nan
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90505, USA
    Exp Mol Pathol 78:1-9. 2005
    ..These results indicate that VCP plays an important role in inducing MB formation, probably through its molecular chaperone function in the ubiquitin-proteasome system (UPS)...
  14. ncbi request reprint The p105/50 NF-kappaB pathway is essential for Mallory body formation
    Li Nan
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90502, USA
    Exp Mol Pathol 78:198-206. 2005
    ..The results indicate that the p105 NF-kappaB pathway which putatively regulates ERK at both the transcriptional and post-translational levels regulates MB formation by way of changes in gene expression...
  15. pmc SAMe prevents the up regulation of toll-like receptor signaling in Mallory-Denk body forming hepatocytes
    Fawzia Bardag-Gorce
    LABioMed at Harbor UCLA Medical Center, Torrance CA 90502, USA
    Exp Mol Pathol 88:376-9. 2010
    ..INFgamma stimulates the up regulation of TLR2. The ability of SAMe feeding to prevent TLR signaling up regulation has not been previously described...
  16. ncbi request reprint Proteasome inhibition induces cytokeratin accumulation in vivo
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 76:83-9. 2004
    ..Accumulation of cytokeratin in this way may ultimately lead to Mallory body formation as seen in alcoholic hepatitis...
  17. pmc S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver
    Fawzia Bardag-Gorce
    Department of Pathology, LABioMed Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 89:217-21. 2010
    ....
  18. pmc Histone acetyltransferase p300 modulates gene expression in an epigenetic manner at high blood alcohol levels
    Fawzia Bardag-Gorce
    Department of Pathology, LA Biomed Research Institute, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 82:197-202. 2007
    ..beta-Catenin was increased in the nuclear extract at the UAL troughs, where increased gene expression was absent. The increase in gene expression at the peaks was due, in part, to increased acetylation of histone 3 at lysine 9...
  19. ncbi request reprint The role of the ubiquitin-proteasome pathway in the formation of mallory bodies
    Fawzia Bardag-Gorce
    Department of Pathology and Medicine, Harbor UCLA Medical Center, Torrance, California 90509, USA
    Exp Mol Pathol 73:75-83. 2002
    ..In conclusion, the results support the concept that Mallory bodies are aggresomes which form as the result of the failure of the ubiquitin-proteasome complex to adequately eliminate cytokeratins destined for proteolysis...
  20. pmc S-adenosylmethionine prevents Mallory Denk body formation in drug-primed mice by inhibiting the epigenetic memory
    Jun Li
    Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Hepatology 47:613-24. 2008
    ..No evidence for the involvement of oxidative stress in induction of the memory was found. The molecular memory included the up-regulation of the expression of genes associated with the development of liver cell preneoplasia...
  21. ncbi request reprint Microarray analysis of gene expression in the liver during the urinary ethanol cycle in rats fed ethanol intragastrically at a constant rate
    Barbara A French
    Department of Pathology, Harbor UCLA Medical Center and LABioMed Research Institute, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 79:87-94. 2005
    ..For instance, the importance of blood alcohol levels at the time that the assays were performed, profoundly changed the gene expression, protein level, and protein phosphorylation level profiles...
  22. pmc Betaine prevents Mallory-Denk body formation in drug-primed mice by epigenetic mechanisms
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 86:77-86. 2009
    ..The results further support the concept that MDB formation is the result of an epigenetic phenomenon, where a change in methionine metabolism causes global gene expression changes in hepatocytes...
  23. pmc Mallory body formation is associated with epigenetic phenotypic change in hepatocytes in vivo
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 83:160-8. 2007
    ....
  24. pmc The regulation of non-coding RNA expression in the liver of mice fed DDC
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 87:12-9. 2009
    ..The dysregulation of ncRNA in MDB forming liver cells has been observed for the first time in drug-primed mice associated with liver preneoplastic foci and tumors...
  25. pmc Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically
    Joan Oliva
    Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 W Carson St Torrance, CA 90502, USA
    World J Gastroenterol 15:705-12. 2009
    ..To examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms...
  26. ncbi request reprint Mallory body forming cells express the preneoplastic hepatocyte phenotype
    Li Nan
    Harbor UCLA Medical Center, Department of Pathology, Los Angeles Biomedical Research Institute, 1000 W Carson St, Torrance, CA 90502, USA
    Exp Mol Pathol 80:109-18. 2006
    ..Thus, the tumor markers used to identify hepatocellular carcinoma were upregulated in cells forming MBs in vivo and in vitro, suggesting that MB forming cells express preneoplastic phenotypic features...
  27. ncbi request reprint Gene expression patterns of the liver in response to alcohol: in vivo and in vitro models compared
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 80:241-51. 2006
    ..These two enzymes have antioxidant effects. In summary, remarkably similar responses to high alcohol levels in the form of changes in gene expression pathways were found in the in vivo and in vitro models tested...
  28. ncbi request reprint The proteasome inhibitor, PS-341, causes cytokeratin aggresome formation
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 76:9-16. 2004
    ..At the same time, the cells became dissociated from each other, however. The results simulated MB formation. MBs differ from cytokeratin aggresomes both morphologically and in ultrastructure...
  29. ncbi request reprint Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease
    Fawzia Bardag-Gorce
    Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Life Sci 77:2594-602. 2005
    ..P62 protein levels were also increased in the purified proteasome fraction of rats given PS-341. This data indicates that modifications in P62 occur due to proteasome inhibition in experimental alcoholic liver disease...
  30. ncbi request reprint Hyperphosphorylation of rat liver proteasome subunits: the effects of ethanol and okadaic acid are compared
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90502, USA
    Life Sci 75:585-97. 2004
    ..In conclusion hyperphosphorylation of the proteasome subunits occurs in the ethanol treated proteasomal subunits which could be one mechanism of the inhibition of the 26S proteasome caused by ethanol feeding...
  31. ncbi request reprint p62 is involved in the mechanism of Mallory body formation
    Li Nan
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 77:168-75. 2004
    ..Overexpression of p62 in normal mouse hepatocytes induced MB-like aggresomes that were stained by Ub but not by CK8. The results indicate that p62 is involved in the mechanism of MB formation...
  32. ncbi request reprint Retinoid X receptor alpha regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver
    Yong Wu
    Department of Pathology, Harbor University of California Los Angeles Research and Education Institute, Torrance, USA
    Mol Pharmacol 65:550-7. 2004
    ..Regulation of hepatic GSH levels by RXRalpha is essential to protect hepatocytes from oxidative stress, whereas up-regulation of phase I drug metabolism genes by RXRalpha may render the liver more sensitive to APAP-induced toxicity...
  33. pmc Protective effect of quercetin, EGCG, catechin and betaine against oxidative stress induced by ethanol in vitro
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 90:295-9. 2011
    ..In conclusion, the in vitro model of oxidative stress induced by ethanol provided evidence that all 4 agents tested prevented some aspect of liver cell injury caused by ethanol...
  34. pmc Alcohol, nutrition and liver cancer: role of Toll-like receptor signaling
    Samuel W French
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    World J Gastroenterol 16:1344-8. 2010
    ..It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases...
  35. ncbi request reprint Liver hypoxia and lack of recovery after reperfusion at high blood alcohol levels in the intragastric feeding model of alcohol liver disease
    Jun Li
    Department of Pathology, Harbor UCLA Medical Center, Torrance, CA 90509, USA
    Exp Mol Pathol 77:184-92. 2004
    ..These results support the hypothesis that hypoxia occurs at the peaks of the BAL cycle and recovery from ischemia is impaired at the peaks...
  36. ncbi request reprint The role of laminin-integrin signaling in triggering MB formation. An in vivo and in vitro study
    Yong Wu
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90502, USA
    Exp Mol Pathol 79:1-8. 2005
    ..The data indicate that laminin-integrin signaling which activates ERK, triggered MB formation in vitro, and an inhibitor of the signaling cascade reduced MB formation...
  37. ncbi request reprint The effect of ethanol-induced CYP2E1 on proteasome activity: the role of 4-hydroxynonenal
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90509, USA
    Exp Mol Pathol 78:109-15. 2005
    ..An adduct of 4-HNE formed with the Rpt4 subunit of 26 S could impede the association of 19 S and 20 S and thus account for the observed decrease of proteasomal activity...
  38. ncbi request reprint Mechanism of the alcohol cyclic pattern: role of catecholamines
    Jun Li
    Dept of Pathology, Harbor University of California Los Angeles Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Am J Physiol Gastrointest Liver Physiol 285:G442-8. 2003
    ..In conclusion, catecholamine supplements prevented the UAL cycle by increasing the metabolic rate to the point at which fluctuations in the metabolic rate caused by alcohol were prevented...
  39. ncbi request reprint The importance of cycling of blood alcohol levels in the pathogenesis of experimental alcoholic liver disease in rats
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, Torrance, California 90509, USA
    Gastroenterology 123:325-35. 2002
    ..The question is how the liver differs at the peaks and troughs of the UAL cycle. Hypoxic injury is postulated to occur at the peaks. Therefore, liver injury may be different at the peaks and troughs...
  40. ncbi request reprint Catecholamines are involved in the mechanism of the urinary alcohol level cycle in rats fed ethanol intragastrically at a constant rate
    Jun Li
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Life Sci 75:3043-51. 2004
    ..Phenoxybenzamine, an alpha blocker disrupted the cycle and elevated ethanol to fatal levels. The results indicate that both alpha and beta adrenergic mechanisms are required for the cycle to occur...
  41. pmc Sirt1 is involved in energy metabolism: the role of chronic ethanol feeding and resveratrol
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St Torrance, CA 90509, USA
    Exp Mol Pathol 85:155-9. 2008
    ..However, resveratrol did not reduce the liver pathology caused by chronic ethanol feeding...
  42. pmc S-adenosylmethionine prevents the up regulation of Toll-like receptor (TLR) signaling caused by chronic ethanol feeding in rats
    Joan Oliva
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson St, Torrance, CA 90509, USA
    Exp Mol Pathol 90:239-43. 2011
    ..In this way the proinflammatory response, fibrogenesis, cirrhosis and hepatocellular carcinoma formation due to alcohol liver disease could be prevented by SAMe...
  43. ncbi request reprint Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice
    M Waheed Roomi
    Department of Pathology, Harbor UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA
    Exp Mol Pathol 81:8-14. 2006
    ..These preneoplastic cells selectively proliferate in response to the promoter effects of necrosis-induced liver cell regeneration ("chemical partial hepatectomy")...
  44. doi request reprint Proteasome inhibitor treatment reduced fatty acid, triacylglycerol and cholesterol synthesis
    Joan Oliva
    Dept of Pathology, LA BioMed at Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 93:26-34. 2012
    ....
  45. pmc Gene expression modifications in the liver caused by binge drinking and S-adenosylmethionine feeding. The role of epigenetic changes
    Jun Li
    LABioMed Research Institute at Harbor UCLA Medical Center, 1000 W Carson St, Los Angeles, CA, 90509, USA
    Genes Nutr 5:169-79. 2010
    ..In conclusion, profound changes in gene expression evolved between 3 h and 12 post ethanol bolus. SAMe down regulated these changes in gene expression at 3 h, and less so at 12 h...
  46. ncbi request reprint Ethanol withdrawal induced CYP2E1 degradation in vivo, blocked by proteasomal inhibitor PS-341
    Fawzia Bardag-Gorce
    Department of Pathology, Harbor UCLA Medical Center, 1000 W Carson Street, Torrance, CA 90509, USA
    Free Radic Biol Med 32:17-21. 2002
    ..In ethanol-withdrawn rats injected with PS-341, CYP2E1 remained at the induced level. These results show, for the first time, that the proteasome is responsible for ethanol-induced CYP2E1 degradation in vivo...
  47. pmc S-adenosylmethionine regulates dual-specificity mitogen-activated protein kinase phosphatase expression in mouse and human hepatocytes
    Maria Lauda Tomasi
    Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    Hepatology 51:2152-61. 2010
    ..SAM treatment in Mat1a KO mice for 7 days raised SAM, DUSP1, mRNA and protein levels and lowered proteosomal and ERK activities...
  48. pmc Mallory-Denk body pathogenesis revisited
    Samuel W French
    Samuel W French, Joan Oliva, Barbara A French, Jun Li, Fawzia Bardag Gorce, Department of Pathology, Harbor UCLA Medical Center, CA 90509, United States
    World J Hepatol 2:295-301. 2010
    ..All of these mechanisms are induced by drug toxicity, and are prevented by feeding the methyl donors SAMe and betaine, supporting the epigenetic response of MDB formation...
  49. pmc Delta-aminolevulinic dehydratase is a proteasome interacting protein
    Fawzia Bardag-Gorce
    Harbor UCLA Medical Center, Torrance, CA 90502, USA
    Exp Mol Pathol 91:485-9. 2011
    ..This indicates that ALAD may play a significant role in regulating proteasome activity. The data supports the hypothesis that ALAD, an important enzyme for heme synthesis, is also important as a proteasome interacting protein...