메뉴 건너뛰기




Volumn 277, Issue 6 40-6, 1999, Pages

Hepatic fibronectin matrix turnover in rats: Involvement of the asialoglycoprotein receptor

Author keywords

Extracellular matrix proteins; Galactose; Hepatocyte receptors; Liver

Indexed keywords

ASIALOGLYCOPROTEIN RECEPTOR; FIBRONECTIN; SCLEROPROTEIN;

EID: 0033385965     PISSN: 01931857     EISSN: None     Source Type: Journal    
DOI: 10.1152/ajpgi.1999.277.6.g1189     Document Type: Article
Times cited : (21)

References (55)
  • 1
    • 0023819775 scopus 로고
    • Extracellular matrix assembly of cell-derived and plasma-derived fibronectins by substrate-attached fibroblasts
    • Allio, A. E., and P. J. McKeown-Longo. Extracellular matrix assembly of cell-derived and plasma-derived fibronectins by substrate-attached fibroblasts. J. Cell. Physiol. 135: 459-466, 1988.
    • (1988) J. Cell. Physiol. , vol.135 , pp. 459-466
    • Allio, A.E.1    McKeown-Longo, P.J.2
  • 2
    • 0020021127 scopus 로고
    • Carbohydrate-specific receptors of the liver
    • Ashwell, G., and J. Harford. Carbohydrate-specific receptors of the liver. Annu. Rev. Biochem. 51: 531-554, 1982.
    • (1982) Annu. Rev. Biochem. , vol.51 , pp. 531-554
    • Ashwell, G.1    Harford, J.2
  • 3
    • 0016322758 scopus 로고
    • The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins
    • Ashwell, G., and A. G. Morell. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv. Enzymol. Relat. Areas Mol. Biol. 41: 99-128, 1974.
    • (1974) Adv. Enzymol. Relat. Areas Mol. Biol. , vol.41 , pp. 99-128
    • Ashwell, G.1    Morell, A.G.2
  • 6
    • 0025822473 scopus 로고
    • Kinetics of plasma fibronectin: Increased lung tissue incorporation after postoperative bacteremia
    • Regulatory Integrative Comp. Physiol. 29
    • Charash, W. E., P. A. Vincent, P. J. McKeown-Longo, T. M. Saba, E. Lewis, and M. A. Lewis. Kinetics of plasma fibronectin: increased lung tissue incorporation after postoperative bacteremia. Am. J. Physiol. 260 (Regulatory Integrative Comp. Physiol. 29): R553-R562, 1991.
    • (1991) Am. J. Physiol. , vol.260
    • Charash, W.E.1    Vincent, P.A.2    McKeown-Longo, P.J.3    Saba, T.M.4    Lewis, E.5    Lewis, M.A.6
  • 8
    • 0016180377 scopus 로고
    • Galactosamine hepatitis: Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death
    • Decker, K., and D. Keppler. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev. Physiol. Biochem. Pharmacol. 71: 78-106, 1974.
    • (1974) Rev. Physiol. Biochem. Pharmacol. , vol.71 , pp. 78-106
    • Decker, K.1    Keppler, D.2
  • 9
    • 0015827011 scopus 로고
    • The regulation of pyrimidine nucleotide level and its role in experimental hepatitis
    • Decker, K., D. Keppler, and J. Pausch. The regulation of pyrimidine nucleotide level and its role in experimental hepatitis Adv. Enzyme Regul. 11: 205-230, 1973.
    • (1973) Adv. Enzyme Regul. , vol.11 , pp. 205-230
    • Decker, K.1    Keppler, D.2    Pausch, J.3
  • 10
    • 0020841996 scopus 로고
    • Kinetics of endogenously labeled plasma fibronectin: Incorporation into tissues
    • Regulatory Integrative Comp. Physiol. 14
    • Deno, D. C., T. M. Saba, and E. P. Lewis. Kinetics of endogenously labeled plasma fibronectin: incorporation into tissues. Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 14): R564-R575, 1983.
    • (1983) Am. J. Physiol. , vol.245
    • Deno, D.C.1    Saba, T.M.2    Lewis, E.P.3
  • 11
    • 0016772868 scopus 로고
    • Early, reversible plasma membrane injury in galactosamine-induced liver cell death
    • El-Mofty, S. K., M.C. Scrutton, A. Serroni, C. Nicolini, and J. L. Farber. Early, reversible plasma membrane injury in galactosamine-induced liver cell death. Am. J. Pathol. 79: 579-596, 1975.
    • (1975) Am. J. Pathol. , vol.79 , pp. 579-596
    • El-Mofty, S.K.1    Scrutton, M.C.2    Serroni, A.3    Nicolini, C.4    Farber, J.L.5
  • 12
    • 0015831726 scopus 로고
    • Prevention of galactosamine-induced liver cell necrosis by uridine
    • Farber, G. A. L., G. Gill, and Y. Konishi. Prevention of galactosamine-induced liver cell necrosis by uridine. Am. J. Pathol. 72: 53-62, 1973.
    • (1973) Am. J. Pathol. , vol.72 , pp. 53-62
    • Farber, G.A.L.1    Gill, G.2    Konishi, Y.3
  • 13
    • 0023514563 scopus 로고
    • Adhesive interactions and the metabolic activity of hepatocytes
    • Hughes, R. C., and S. C. Stamatoglou. Adhesive interactions and the metabolic activity of hepatocytes. J. Cell Sci. Suppl. 8: 273-291, 1987.
    • (1987) J. Cell Sci. Suppl. , vol.8 , pp. 273-291
    • Hughes, R.C.1    Stamatoglou, S.C.2
  • 14
    • 0004043397 scopus 로고
    • New York: Springer-Verlag
    • Hynes, R. O. Fibronectins. New York: Springer-Verlag, 1990.
    • (1990) Fibronectins
    • Hynes, R.O.1
  • 15
    • 0028260934 scopus 로고
    • Hepatocyte matrix interactions
    • Iredale, J. P., and M. J. P. Arthur. Hepatocyte matrix interactions. Gut 35: 729-732, 1994.
    • (1994) Gut , vol.35 , pp. 729-732
    • Iredale, J.P.1    Arthur, M.J.P.2
  • 17
    • 0026348693 scopus 로고
    • Incorporation of circulating fibronectin into various tissues during sepsis: Colocalization with endogenous tissue fibronectin
    • Jin, H. M., P. A. Vincent, W. E. Charash, T. M. Saba, P. McKeown-Longo, F.A. Blumenstock, and E. Lewis. Incorporation of circulating fibronectin into various tissues during sepsis: colocalization with endogenous tissue fibronectin. Exp. Mol. Pathol. 55: 203-216, 1991.
    • (1991) Exp. Mol. Pathol. , vol.55 , pp. 203-216
    • Jin, H.M.1    Vincent, P.A.2    Charash, W.E.3    Saba, T.M.4    McKeown-Longo, P.5    Blumenstock, F.A.6    Lewis, E.7
  • 18
    • 0026504084 scopus 로고
    • Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats
    • Jonker, A. M., F. W. J. Dijkhuis, A. Boes, M. J. Hardonk, and J. Grond. Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats. Hepatology 15: 423-431, 1992.
    • (1992) Hepatology , vol.15 , pp. 423-431
    • Jonker, A.M.1    Dijkhuis, F.W.J.2    Boes, A.3    Hardonk, M.J.4    Grond, J.5
  • 19
    • 0027958462 scopus 로고
    • Immunohistochemical study of hepatic fibrosis induced in rats by multiple galactosamine injections
    • Jonker, A. M., W. J. Dijkhuis, M. J. Hardonk, P. Moerkerk, J. T. Kate, and J. Grond. Immunohistochemical study of hepatic fibrosis induced in rats by multiple galactosamine injections. Hepatology 19: 775-781, 1994.
    • (1994) Hepatology , vol.19 , pp. 775-781
    • Jonker, A.M.1    Dijkhuis, W.J.2    Hardonk, M.J.3    Moerkerk, P.4    Kate, J.T.5    Grond, J.6
  • 20
    • 0014901704 scopus 로고
    • The trapping of uridine phosphates by D-galactosamine, D-glucosamine and 2-deoxy-D-galactose. A study on the mechanism of galactose-amine hepatitis
    • Keppler, D. O. R., J. F. M. Rudigier, E. Bischoff, and F. A. Decker. The trapping of uridine phosphates by D-galactosamine, D-glucosamine and 2-deoxy-D-galactose. A study on the mechanism of galactose-amine hepatitis. Eur. J. Biochem. 17: 246-253, 1970.
    • (1970) Eur. J. Biochem. , vol.17 , pp. 246-253
    • Keppler, D.O.R.1    Rudigier, J.F.M.2    Bischoff, E.3    Decker, F.A.4
  • 21
    • 0027765620 scopus 로고
    • Cooperation of Ito cells and hepatocytes in the deposition of an extracellular matrix in vitro
    • Loreal, O., F. Levavasseur, C. Fromaget, D. Gros, A. Guillouzo, and B. Clement. Cooperation of Ito cells and hepatocytes in the deposition of an extracellular matrix in vitro. Am. J. Pathol. 143: 538-544, 1993.
    • (1993) Am. J. Pathol. , vol.143 , pp. 538-544
    • Loreal, O.1    Levavasseur, F.2    Fromaget, C.3    Gros, D.4    Guillouzo, A.5    Clement, B.6
  • 22
    • 0021131587 scopus 로고
    • The hepatic extracellular matrix. I. Electron immuno-histochemical studies in normal rat liver
    • Martinez-Hernandez, A. The hepatic extracellular matrix. I. Electron immuno-histochemical studies in normal rat liver. Lab. Invest. 51: 57-74, 1984.
    • (1984) Lab. Invest. , vol.51 , pp. 57-74
    • Martinez-Hernandez, A.1
  • 23
    • 0025882635 scopus 로고
    • The extracellular matrix in hepatic regeneration: Localization of collagen types I, III, IV, laminin and fibronectin
    • Martinez-Hernandez, A., F. M. Delgado, and P. S. Amenta. The extracellular matrix in hepatic regeneration: localization of collagen types I, III, IV, laminin and fibronectin. Lab. Invest. 64: 157-166, 1991.
    • (1991) Lab. Invest. , vol.64 , pp. 157-166
    • Martinez-Hernandez, A.1    Delgado, F.M.2    Amenta, P.S.3
  • 24
    • 0020601855 scopus 로고
    • Binding of plasma flbronectin to cell layers of human skin fibroblasts
    • McKeown-Longo, P. J., and D. F. Mosher. Binding of plasma flbronectin to cell layers of human skin fibroblasts. J. Cell Biol. 97: 466-472, 1983.
    • (1983) J. Cell Biol. , vol.97 , pp. 466-472
    • McKeown-Longo, P.J.1    Mosher, D.F.2
  • 25
    • 0021128653 scopus 로고
    • Mechanism of formation of disulflde-bonded multimers of plasma fibronectin in cell layers of cultured human fibroblasts
    • McKeown-Longo, P. J., and D. F. Mosher. Mechanism of formation of disulflde-bonded multimers of plasma fibronectin in cell layers of cultured human fibroblasts. J. Biol. Chem. 259: 12210-12215, 1984.
    • (1984) J. Biol. Chem. , vol.259 , pp. 12210-12215
    • McKeown-Longo, P.J.1    Mosher, D.F.2
  • 26
    • 0021926873 scopus 로고
    • Interaction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts
    • McKeown-Longo, P. J., and D. F. Mosher. Interaction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts. J. Cell Biol. 100: 364-374, 1985.
    • (1985) J. Cell Biol. , vol.100 , pp. 364-374
    • McKeown-Longo, P.J.1    Mosher, D.F.2
  • 29
  • 30
    • 0020658940 scopus 로고
    • In vivo quantification of receptor-mediated uptake of asialogylocprotein by rat liver
    • Pardridge, W. M., A. J. Van Herle, R. T. Naruse, G. Fierer, and A. Costin. In vivo quantification of receptor-mediated uptake of asialogylocprotein by rat liver. J. Biol. Chem. 258: 990-994, 1983.
    • (1983) J. Biol. Chem. , vol.258 , pp. 990-994
    • Pardridge, W.M.1    Van Herle, A.J.2    Naruse, R.T.3    Fierer, G.4    Costin, A.5
  • 31
    • 0023062492 scopus 로고
    • D-Galactosamine induced changes in rat liver plasma membranes lipid composition and some enzyme activities
    • Petovka, D. H., A. B. Momchilova, T. T. Markovska, and K. S. Koumanov. D-Galactosamine induced changes in rat liver plasma membranes lipid composition and some enzyme activities. Int. J. Biochem. 19: 289-291, 1987.
    • (1987) Int. J. Biochem. , vol.19 , pp. 289-291
    • Petovka, D.H.1    Momchilova, A.B.2    Markovska, T.T.3    Koumanov, K.S.4
  • 33
    • 0018863570 scopus 로고
    • Hepatotoxicity of D-galactosamine in the isolated perfused rat liver
    • Rasenack, J., H. K. Koch, J. Nowack, R. Lesch, and K. Decker. Hepatotoxicity of D-galactosamine in the isolated perfused rat liver. Exp. Mol. Pathol. 32: 264-275, 1980.
    • (1980) Exp. Mol. Pathol. , vol.32 , pp. 264-275
    • Rasenack, J.1    Koch, H.K.2    Nowack, J.3    Lesch, R.4    Decker, K.5
  • 34
    • 0029836023 scopus 로고    scopus 로고
    • Reduced in vivo plasma fibronectin content of lung matrix during postoperative sepsis
    • Lung Cell. Mol. Physiol. 15
    • Rebres, R. A., E. Cho, R. F. Rotundo, and T. M. Saba. Reduced in vivo plasma fibronectin content of lung matrix during postoperative sepsis. Am. J. Physiol. 271 (Lung Cell. Mol. Physiol. 15): L409-L418, 1996.
    • (1996) Am. J. Physiol. , vol.271
    • Rebres, R.A.1    Cho, E.2    Rotundo, R.F.3    Saba, T.M.4
  • 35
    • 0029608747 scopus 로고
    • Extracellular matrix incorporation of normal and NEM-alkylated fibronectin: Liver and spleen deposition
    • Gastrointest. Liver Physiol. 32
    • Rebres, R. A., P. J. McKeown-Longo, P. A. Vincent, E. Cho, and T. M. Saba. Extracellular matrix incorporation of normal and NEM-alkylated fibronectin: liver and spleen deposition. Am. J. Physiol. 269 (Gastrointest. Liver Physiol. 32): G902-G912, 1995.
    • (1995) Am. J. Physiol. , vol.269
    • Rebres, R.A.1    McKeown-Longo, P.J.2    Vincent, P.A.3    Cho, E.4    Saba, T.M.5
  • 36
    • 0031903843 scopus 로고    scopus 로고
    • Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor: Possible pathway for fibronectin deposition and turnover in the rat liver
    • Rotundo, R. F., R. A. Rebres, P. J. McKeown-Longo, F. A. Blumenstock, and T. M. Saba. Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor: possible pathway for fibronectin deposition and turnover in the rat liver. Hepatology 28: 475-485, 1998.
    • (1998) Hepatology , vol.28 , pp. 475-485
    • Rotundo, R.F.1    Rebres, R.A.2    McKeown-Longo, P.J.3    Blumenstock, F.A.4    Saba, T.M.5
  • 37
    • 0020015466 scopus 로고
    • Plasma fibronectin and hepatic Kupffer cell function
    • edited by H. Popper and F. Schaffner. New York: Grune & Stratton
    • Saba, T. M. Plasma fibronectin and hepatic Kupffer cell function. In: Progress in Liver Disease, edited by H. Popper and F. Schaffner. New York: Grune & Stratton, 1982, p. 109-131.
    • (1982) Progress in Liver Disease , pp. 109-131
    • Saba, T.M.1
  • 38
    • 0005958601 scopus 로고
    • Fibronectin: Role in phagocytic host defenses and lung vascular integrity
    • edited by S. Carsons. Boca Raton, FL: CRC
    • Saba, T. M. Fibronectin: role in phagocytic host defenses and lung vascular integrity. In: Fibronectin in Health and Disease, edited by S. Carsons. Boca Raton, FL: CRC, 1989, p. 49-68.
    • (1989) Fibronectin in Health and Disease , pp. 49-68
    • Saba, T.M.1
  • 39
    • 0019417537 scopus 로고
    • Decrease of hepatic binding protein specific for asialoglycoproteins with accumulation of serum asialoglycoproteins in galactosamine-treated rats
    • Sawamura, T., S. Kawasato, Y. Shiozaki, Y. Sameshima, H. Nakada, and Y. Tashiro. Decrease of hepatic binding protein specific for asialoglycoproteins with accumulation of serum asialoglycoproteins in galactosamine-treated rats. Gastroenterology 81: 527-533, 1981.
    • (1981) Gastroenterology , vol.81 , pp. 527-533
    • Sawamura, T.1    Kawasato, S.2    Shiozaki, Y.3    Sameshima, Y.4    Nakada, H.5    Tashiro, Y.6
  • 40
    • 0021192483 scopus 로고
    • The hepatic asialoglycoprotein receptor
    • Schwartz, A. L. The hepatic asialoglycoprotein receptor. CRC Crit. Rev. Biochem. 16: 207-233, 1995.
    • (1995) CRC Crit. Rev. Biochem. , vol.16 , pp. 207-233
    • Schwartz, A.L.1
  • 41
    • 0025186227 scopus 로고
    • Identification of a novel glycoprotein (AGp110) involved in interactions of rat liver parenchymal cells with fibronectin
    • Stamatoglou, S. C., R.-C. Ge, G. Mills, T. D. Butters, F. Zaidi, and R. C. Hughes. Identification of a novel glycoprotein (AGp110) involved in interactions of rat liver parenchymal cells with fibronectin. J. Cell Biol. 111: 2117-2127, 1990.
    • (1990) J. Cell Biol. , vol.111 , pp. 2117-2127
    • Stamatoglou, S.C.1    Ge, R.-C.2    Mills, G.3    Butters, T.D.4    Zaidi, F.5    Hughes, R.C.6
  • 43
    • 0023022612 scopus 로고
    • Modulation of protein synthesis and secretion by substratum in primary cultures of rat hepatocytes
    • Sudhakaran, P. R., S. Stamatoglou, and R. C. Hughes. Modulation of protein synthesis and secretion by substratum in primary cultures of rat hepatocytes. Exp. Cell Res. 167: 505-516, 1986.
    • (1986) Exp. Cell Res. , vol.167 , pp. 505-516
    • Sudhakaran, P.R.1    Stamatoglou, S.2    Hughes, R.C.3
  • 44
    • 0027351324 scopus 로고
    • Extracellular sialidases
    • Sweeley, C. C. Extracellular sialidases. Adv. Lipid Res. 26: 235-252, 1993.
    • (1993) Adv. Lipid Res. , vol.26 , pp. 235-252
    • Sweeley, C.C.1
  • 45
    • 0019294102 scopus 로고
    • Structural studies of the sugar chains of cold-insoluble globulin isolated from human plasma
    • Takasaki, S., K. Yamashita, K. Suzuki, and A. Kobata. Structural studies of the sugar chains of cold-insoluble globulin isolated from human plasma. J. Biochem. (Tokyo) 88: 1587-1594, 1980.
    • (1980) J. Biochem. (Tokyo) , vol.88 , pp. 1587-1594
    • Takasaki, S.1    Yamashita, K.2    Suzuki, K.3    Kobata, A.4
  • 46
    • 0023732740 scopus 로고
    • The role of liver endothelium in the transfer of iron from transferrin to the hepatocyte
    • Tavassoli, M. The role of liver endothelium in the transfer of iron from transferrin to the hepatocyte. Ann. NY Acad. Sci. 526: 83-92, 1988.
    • (1988) Ann. NY Acad. Sci. , vol.526 , pp. 83-92
    • Tavassoli, M.1
  • 47
    • 0022551211 scopus 로고
    • Liver endothelium mediates the hepatocyte's uptake of ceruloplasmin
    • Tavassoli, M., T. Kishimoto, and M. Kataoka. Liver endothelium mediates the hepatocyte's uptake of ceruloplasmin. J. Cell Biol. 102: 1298-1303, 1986.
    • (1986) J. Cell Biol. , vol.102 , pp. 1298-1303
    • Tavassoli, M.1    Kishimoto, T.2    Kataoka, M.3
  • 49
    • 0026742271 scopus 로고
    • Liver endocytosis and Kupfer cells
    • Toth, C. A., and P. Thomas. Liver endocytosis and Kupfer cells. Hepatology 16: 255-266, 1992.
    • (1992) Hepatology , vol.16 , pp. 255-266
    • Toth, C.A.1    Thomas, P.2
  • 50
    • 0026772958 scopus 로고
    • N-glycosylation of serum proteins in disease and its investigation using lectins
    • Turner, G. A. N-glycosylation of serum proteins in disease and its investigation using lectins. Clin. Chim. Acta 208: 149-171, 1992.
    • (1992) Clin. Chim. Acta , vol.208 , pp. 149-171
    • Turner, G.A.1
  • 51
    • 0024844603 scopus 로고
    • Contribution of hepatic fibronectin synthesis to regulation of plasma fibronectin
    • Regulatory Integrative Comp. Physiol. 26
    • Vincent, P. A., T. M. Saba, E. Lewis, and E. Cho. Contribution of hepatic fibronectin synthesis to regulation of plasma fibronectin. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R1406-R1416, 1989.
    • (1989) Am. J. Physiol. , vol.257
    • Vincent, P.A.1    Saba, T.M.2    Lewis, E.3    Cho, E.4
  • 52
    • 0027204063 scopus 로고
    • Incorporation of fibronectin into matrix decreases TNF-induced increase in endothelial monolayer permeability
    • Lung Cell. Mol. Phvsiol. 9
    • Wheatley, E. M., P. J. McKeown-Longo, P. A. Vincent, and T. M. Saba. Incorporation of fibronectin into matrix decreases TNF-induced increase in endothelial monolayer permeability. Am. J. Physiol. 265 (Lung Cell. Mol. Phvsiol. 9): L148-L157, 1993.
    • (1993) Am. J. Physiol. , vol.265
    • Wheatley, E.M.1    McKeown-Longo, P.J.2    Vincent, P.A.3    Saba, T.M.4
  • 53
    • 0027471907 scopus 로고
    • Effect of fibronectin on permeability of normal and TNF-treated lung endothelial cell monolayers
    • Regulatory Integrative Comp. Physiol. 33
    • Wheatley, E. M., P. A. Vincent, P. J. McKeown-Longo, and T. M. Saba. Effect of fibronectin on permeability of normal and TNF-treated lung endothelial cell monolayers. Am. J. Physiol. 264 (Regulatory Integrative Comp. Physiol. 33): R90-R96, 1993.
    • (1993) Am. J. Physiol. , vol.264
    • Wheatley, E.M.1    Vincent, P.A.2    McKeown-Longo, P.J.3    Saba, T.M.4
  • 54
    • 0021718330 scopus 로고
    • Swainsonine inhibits glycoprotein degradation by isolated rat liver lysosomes
    • Winkler, J. R., and H. L. Segal. Swainsonine inhibits glycoprotein degradation by isolated rat liver lysosomes. J. Biol. Chem. 259: 15369-15372, 1984.
    • (1984) J. Biol. Chem. , vol.259 , pp. 15369-15372
    • Winkler, J.R.1    Segal, H.L.2
  • 55
    • 0018072526 scopus 로고
    • Methylation analysis of the carbohydrate portion of fibronectin isolated from human plasma
    • Wrann, M. Methylation analysis of the carbohydrate portion of fibronectin isolated from human plasma. Biochem. Biophys. Res. Commun. 84: 269-274, 1978.
    • (1978) Biochem. Biophys. Res. Commun. , vol.84 , pp. 269-274
    • Wrann, M.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.