메뉴 건너뛰기




Volumn 16, Issue 5, 2014, Pages 392-406

Psammaplin A improves development and quality of somatic cell nuclear transfer mouse embryos

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHALASIN B; DNA; HISTONE; HISTONE DEACETYLASE INHIBITOR; LATRUNCULIN A; OCTAMER TRANSCRIPTION FACTOR 4; PSAMMAPLIN A; TRANSCRIPTION FACTOR CDX2; TRANSCRIPTION FACTOR NANOG; UNCLASSIFIED DRUG; VALPROIC ACID; DISULFIDE; TYROSINE;

EID: 84907261724     PISSN: 21524971     EISSN: 21524998     Source Type: Journal    
DOI: 10.1089/cell.2014.0012     Document Type: Article
Times cited : (9)

References (53)
  • 1
    • 37349061341 scopus 로고    scopus 로고
    • A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells
    • Ahn, M.Y., Jung, J.H., Na, Y.J., and Kim, H.S. (2008). A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells. Gynecol. Oncol. 108, 27-33.
    • (2008) Gynecol. Oncol. , vol.108 , pp. 27-33
    • Ahn, M.Y.1    Jung, J.H.2    Na, Y.J.3    Kim, H.S.4
  • 2
    • 84897481535 scopus 로고    scopus 로고
    • Formin' actin in the nucleus
    • Baarlink, C., and Grosse, R. (2014). Formin' actin in the nucleus. Nucleus 5, 1-6.
    • (2014) Nucleus , vol.5 , pp. 1-6
    • Baarlink, C.1    Grosse, R.2
  • 5
    • 0037093508 scopus 로고    scopus 로고
    • Oct4 distribution and level in mouse clones: Consequences for pluripotency
    • Boiani, M., Eckardt, S., Schöler, H.R., and Mclaughlin, K.J. (2002). Oct4 distribution and level in mouse clones: Consequences for pluripotency. Genes Dev. 16, 1209-1219.
    • (2002) Genes Dev. , vol.16 , pp. 1209-1219
    • Boiani, M.1    Eckardt, S.2    Schöler, H.R.3    McLaughlin, K.J.4
  • 6
    • 25444520522 scopus 로고    scopus 로고
    • Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones: Distinct developmental potentials in different culture environments
    • Boiani, M., Gentile, L., Gambles, V. V, Cavaleri, F., Redi, C.A., and Schöler, H.R. (2005). Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones: Distinct developmental potentials in different culture environments. Stem Cells 23, 1089-1104.
    • (2005) Stem Cells , vol.23 , pp. 1089-1104
    • Boiani, M.1    Gentile, L.2    Gambles, V.V.3    Cavaleri, F.4    Redi, C.A.5    Schöler, H.R.6
  • 8
    • 84875165863 scopus 로고    scopus 로고
    • Epigenetic programming and reprogramming during development
    • Cantone, I., and Fisher, A.G. (2013). Epigenetic programming and reprogramming during development. Nat. Struct. Mol. Biol. 20, 282-289.
    • (2013) Nat. Struct. Mol. Biol. , vol.20 , pp. 282-289
    • Cantone, I.1    Fisher, A.G.2
  • 10
    • 84865693989 scopus 로고    scopus 로고
    • Mouse ooplasm confers context-specific reprogramming capacity
    • Chan, M.M., Smith, Z.D., Egli, D., Regev, A., and Meissner, A. (2012). Mouse ooplasm confers context-specific reprogramming capacity. Nat. Genet. 44, 978-980.
    • (2012) Nat. Genet. , vol.44 , pp. 978-980
    • Chan, M.M.1    Smith, Z.D.2    Egli, D.3    Regev, A.4    Meissner, A.5
  • 11
    • 0024407119 scopus 로고
    • An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro
    • Chatot, C.L., Ziomek, C.A., Bavister, B.D., Lewis, J.L., and Torres, I. (1989). An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J. Reprod. Fertil. 86, 679-688.
    • (1989) J. Reprod. Fertil. , vol.86 , pp. 679-688
    • Chatot, C.L.1    Ziomek, C.A.2    Bavister, B.D.3    Lewis, J.L.4    Torres, I.5
  • 12
    • 0037775594 scopus 로고    scopus 로고
    • Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos
    • Chung, Y.G., Ratnam, S., Chaillet, J.R., and Latham, K,E. (2003). Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod. 69, 146-153.
    • (2003) Biol Reprod. , vol.69 , pp. 146-153
    • Chung, Y.G.1    Ratnam, S.2    Chaillet, J.R.3    Latham, K.E.4
  • 13
    • 77955162628 scopus 로고    scopus 로고
    • Comparison between the effects of valproic acid and trichostatin A on the in vitro development, blastocyst quality, and full-term development of mouse somatic cell nuclear transfer embryos
    • Costa-Borges, N., Santalo, J., and Ibañez, E. (2010). Comparison between the effects of valproic acid and trichostatin A on the in vitro development, blastocyst quality, and full-term development of mouse somatic cell nuclear transfer embryos. Cell. Reprogram. 12, 1-10.
    • (2010) Cell. Reprogram. , vol.12 , pp. 1-10
    • Costa-Borges, N.1    Santalo, J.2    Ibañez, E.3
  • 14
    • 0035923602 scopus 로고    scopus 로고
    • Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos
    • Dean, W., Santos, F., Stojkovic, M., Zakhartchenko, V., Walter, J., Wolf, E., and Reik, W. (2001). Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos. Proc. Natl. Acad. Sci. USA 98, 13734-13738.
    • (2001) Proc. Natl. Acad. Sci. USA , vol.98 , pp. 13734-13738
    • Dean, W.1    Santos, F.2    Stojkovic, M.3    Zakhartchenko, V.4    Walter, J.5    Wolf, E.6    Reik, W.7
  • 15
    • 0034968451 scopus 로고    scopus 로고
    • Emerging connections between DNA methylation and histone acetylation
    • Dobosy, J.R., and Selker, E.U. (2001). Emerging connections between DNA methylation and histone acetylation. Cell. Mol. Life Sci. 58, 721-727.
    • (2001) Cell. Mol. Life Sci. , vol.58 , pp. 721-727
    • Dobosy, J.R.1    Selker, E.U.2
  • 16
    • 0041861033 scopus 로고    scopus 로고
    • Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-2¢-deoxycytidine
    • Enright, B.P., Kubota, C., Yang, X., and Tian, X.C. (2003). Epigenetic characteristics and development of embryos cloned from donor cells treated by trichostatin A or 5-aza-2¢-deoxycytidine. Biol. Reprod. 69, 896-901.
    • (2003) Biol. Reprod. , vol.69 , pp. 896-901
    • Enright, B.P.1    Kubota, C.2    Yang, X.3    Tian, X.C.4
  • 19
    • 84859149166 scopus 로고    scopus 로고
    • Genes are often sheltered from the global histone hyperacetylation induced by HDAC inhibitors
    • Halsall, J., Gupta, V., O'Neill, L.P., Turner, B.M., and Nightingale, K.P. (2012). Genes are often sheltered from the global histone hyperacetylation induced by HDAC inhibitors. PloS One 7, e33453.
    • (2012) PloS One , vol.7 , pp. e33453
    • Halsall, J.1    Gupta, V.2    O'Neill, L.P.3    Turner, B.M.4    Nightingale, K.P.5
  • 20
    • 83255166473 scopus 로고    scopus 로고
    • Histone deacetylase inhibitor significantly improved the cloning efficiency of porcine somatic cell nuclear transfer embryos
    • Huang, Y., Tang, X., Xie, W., Zhou, Y., Li, D., Yao, C., Zhou, Y., Zhu, J., Lai, L., Ouyang, H., and Pang, D. (2011). Histone deacetylase inhibitor significantly improved the cloning efficiency of porcine somatic cell nuclear transfer embryos. Cell. Reprogram. 13, 513-520.
    • (2011) Cell. Reprogram. , vol.13 , pp. 513-520
    • Huang, Y.1    Tang, X.2    Xie, W.3    Zhou, Y.4    Li, D.5    Yao, C.6    Zhou, Y.7    Zhu, J.8    Lai, L.9    Ouyang, H.10    Pang, D.11
  • 22
    • 84876578768 scopus 로고    scopus 로고
    • Valproic acid treatment from the 4-cell stage improves Oct4 expression and nuclear distribution of histone H3K27me3 in mouse cloned blastocysts
    • Isaji, Y., Murata, M., Takaguchi, N., Mukai, T., Tajima, Y., Imai, H., and Yamada, M. (2013). Valproic acid treatment from the 4-cell stage improves Oct4 expression and nuclear distribution of histone H3K27me3 in mouse cloned blastocysts. J. Reprod. Dev. 59, 196-204.
    • (2013) J. Reprod. Dev. , vol.59 , pp. 196-204
    • Isaji, Y.1    Murata, M.2    Takaguchi, N.3    Mukai, T.4    Tajima, Y.5    Imai, H.6    Yamada, M.7
  • 25
    • 0036500481 scopus 로고    scopus 로고
    • Limited demethylation leaves mosaic-type methylation states in cloned bovine preimplantation embryos
    • Kang, Y.-K., Park, J.S., Koo, D.-B., Choi, Y.-H., Kim, S.-U., Lee, K.-K., and Han, Y.-M. (2002). Limited demethylation leaves mosaic-type methylation states in cloned bovine preimplantation embryos. EMBO J. 21, 1092-1100.
    • (2002) EMBO J. , vol.21 , pp. 1092-1100
    • Kang, Y.-K.1    Park, J.S.2    Koo, D.-B.3    Choi, Y.-H.4    Kim, S.-U.5    Lee, K.-K.6    Han, Y.-M.7
  • 26
    • 0032806308 scopus 로고    scopus 로고
    • Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells
    • Kim, D., Lee, I.S., Jung, J.H., Lee, C.O., and Choi, S.U. (1999a). Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells. Anticancer Res. 19, 4085-4090.
    • (1999) Anticancer Res. , vol.19 , pp. 4085-4090
    • Kim, D.1    Lee, I.S.2    Jung, J.H.3    Lee, C.O.4    Choi, S.U.5
  • 27
    • 0033073547 scopus 로고    scopus 로고
    • Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistant Staphylococcus aureus and the DNA gyrase-inhibitory activity
    • Kim, D., Lee, I.S., Jung, J.H., and Yang, S.I. (1999b). Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistant Staphylococcus aureus and the DNA gyrase-inhibitory activity. Arch. Pharm. Res. 22, 25-29.
    • (1999) Arch. Pharm. Res. , vol.22 , pp. 25-29
    • Kim, D.1    Lee, I.S.2    Jung, J.H.3    Yang, S.I.4
  • 28
    • 33847657556 scopus 로고    scopus 로고
    • Psammaplin A is a natural prodrug that inhibits class i histone deacetylase
    • Kim, D.H., Shin, J., and Kwon, H.J. (2007). Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. Exp. Mol. Med. 39, 47-55.
    • (2007) Exp. Mol. Med. , vol.39 , pp. 47-55
    • Kim, D.H.1    Shin, J.2    Kwon, H.J.3
  • 29
    • 79956083510 scopus 로고    scopus 로고
    • Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos
    • Kim, Y.J., Ahn, K.S., Kim, M., and Shim, H. (2011). Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos. In Vitro Cell. Dev. Biol. Anim. 47, 283-289.
    • (2011) Vitro Cell. Dev. Biol. Anim. , vol.47 , pp. 283-289
    • Kim, Y.J.1    Ahn, K.S.2    Kim, M.3    Shim, H.4
  • 32
    • 54949117927 scopus 로고    scopus 로고
    • Differential acetylation of histone H4 lysine during development of in vitro fertilized, cloned and parthenogenetically activated bovine embryos
    • Maalouf, W.E., Alberio, R., and Campbell, K.H.S. (2008). Differential acetylation of histone H4 lysine during development of in vitro fertilized, cloned and parthenogenetically activated bovine embryos. Epigenetics 3, 199-209.
    • (2008) Epigenetics , vol.3 , pp. 199-209
    • Maalouf, W.E.1    Alberio, R.2    Campbell, K.H.S.3
  • 33
    • 84874305095 scopus 로고    scopus 로고
    • Comparison of three differential mouse blastocyst staining methods
    • Mallol, A., Santaló, J., and Ibáñez, E. (2013). Comparison of three differential mouse blastocyst staining methods. Syst. Biol. Reprod. Med. 1-6.
    • (2013) Syst. Biol. Reprod. Med. , pp. 1-6
    • Mallol, A.1    Santaló, J.2    Ibáñez, E.3
  • 34
    • 0042862983 scopus 로고    scopus 로고
    • Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos
    • Mann, M.R.W., Chung, Y.G., Nolen, L.D., Verona, R.I., Latham, K.E., and Bartolomei, M.S. (2003). Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol. Reprod. 69, 902-914.
    • (2003) Biol. Reprod. , vol.69 , pp. 902-914
    • Mann, M.R.W.1    Chung, Y.G.2    Nolen, L.D.3    Verona, R.I.4    Latham, K.E.5    Bartolomei, M.S.6
  • 35
    • 57149093007 scopus 로고    scopus 로고
    • Cotransfer of parthenogenetic embryos improves the pregnancy and implantation of nuclear transfer embryos in mouse
    • Meng, Q., Wang, M., Stanca, C.A., Bodo, S., and Dinnyes, A. (2008). Cotransfer of parthenogenetic embryos improves the pregnancy and implantation of nuclear transfer embryos in mouse. Cloning Stem Cells 10, 429-434.
    • (2008) Cloning Stem Cells , vol.10 , pp. 429-434
    • Meng, Q.1    Wang, M.2    Stanca, C.A.3    Bodo, S.4    Dinnyes, A.5
  • 36
    • 79955683477 scopus 로고    scopus 로고
    • Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes
    • Miyamoto, K., Pasque, V., Jullien, J., and Gurdon, J.B. (2011). Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes. Genes Dev. 25, 946-958.
    • (2011) Genes Dev. , vol.25 , pp. 946-958
    • Miyamoto, K.1    Pasque, V.2    Jullien, J.3    Gurdon, J.B.4
  • 37
    • 77952318459 scopus 로고    scopus 로고
    • Valproic acid enhances in vitro development and Oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos
    • Miyoshi, K., Mori, H., Mizobe, Y., Akasaka, E., Ozawa, A., Yoshida, M., and Sato,M. (2010).Valproic acid enhances in vitro development and Oct-3/4 expression of miniature pig somatic cell nuclear transfer embryos. Cell. Reprogram. 12, 67-74.
    • (2010) Cell. Reprogram. , vol.12 , pp. 67-74
    • Miyoshi, K.1    Mori, H.2    Mizobe, Y.3    Akasaka, E.4    Ozawa, A.5    Yoshida, M.6    Sato, M.7
  • 39
    • 39449128840 scopus 로고    scopus 로고
    • Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning
    • Niemann, H., Tian, X.C., King, W.A., Lee, R.S. (2008). Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning. Reproduction 135, 151-163.
    • (2008) Reproduction , vol.135 , pp. 151-163
    • Niemann, H.1    Tian, X.C.2    King, W.A.3    Lee, R.S.4
  • 42
    • 33748305875 scopus 로고    scopus 로고
    • Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer
    • Rybouchkin, A., Kato, Y., and Tsunoda, Y. (2006). Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer. Biol. Reprod. 74, 1083-1089.
    • (2006) Biol. Reprod. , vol.74 , pp. 1083-1089
    • Rybouchkin, A.1    Kato, Y.2    Tsunoda, Y.3
  • 43
    • 80052277882 scopus 로고    scopus 로고
    • Oxamflatin significantly improves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNT embryos
    • Su, J., Wang, Y., Li, Y., Li, R., Li, Q., Wu, Y., Quan, F., Liu, J., Guo, Z., and Zhang, Y. (2011). Oxamflatin significantly improves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNT embryos. PLoS One 6, e23805.
    • (2011) PLoS One , vol.6 , pp. e23805
    • Su, J.1    Wang, Y.2    Li, Y.3    Li, R.4    Li, Q.5    Wu, Y.6    Quan, F.7    Liu, J.8    Guo, Z.9    Zhang, Y.10
  • 44
    • 84863489702 scopus 로고    scopus 로고
    • Latrunculin A can improve the birth rate of cloned mice and simplify the nuclear transfer protocol by gently inhibiting actin polymerization
    • Terashita, Y., Wakayama, S., Yamagata, K., Li, C., Sato, E., and Wakayama, T. (2012). Latrunculin A can improve the birth rate of cloned mice and simplify the nuclear transfer protocol by gently inhibiting actin polymerization. Biol. Reprod. 86, 180.
    • (2012) Biol. Reprod. , vol.86 , pp. 180
    • Terashita, Y.1    Wakayama, S.2    Yamagata, K.3    Li, C.4    Sato, E.5    Wakayama, T.6
  • 45
    • 84886242296 scopus 로고    scopus 로고
    • Latrunculin a treatment prevents abnormal chromosome segregation for successful development of cloned embryos
    • Terashita, Y., Yamagata, K., Tokoro, M., Itoi, F., Wakayama, S., Li, C., Sato, E., Tanemura, K., and Wakayama, T. (2013). Latrunculin a treatment prevents abnormal chromosome segregation for successful development of cloned embryos. PLoS One 8, e78380.
    • (2013) PLoS One , vol.8 , pp. e78380
    • Terashita, Y.1    Yamagata, K.2    Tokoro, M.3    Itoi, F.4    Wakayama, S.5    Li, C.6    Sato, E.7    Tanemura, K.8    Wakayama, T.9
  • 46
    • 85006307269 scopus 로고    scopus 로고
    • Simplified technique for differential staining of inner cell mass and trophectoderm cells of mouse and bovine blastocysts
    • Thouas, G.A., Korfiatis, N.A., French, A.J., Jones, G.M., and Trounson, A.O. (2001). Simplified technique for differential staining of inner cell mass and trophectoderm cells of mouse and bovine blastocysts. Reprod. BioMed. Online 3, 25-29.
    • (2001) Reprod. BioMed. Online , vol.3 , pp. 25-29
    • Thouas, G.A.1    Korfiatis, N.A.2    French, A.J.3    Jones, G.M.4    Trounson, A.O.5
  • 47
    • 70149094112 scopus 로고    scopus 로고
    • The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice
    • Van Thuan, N., Bui, H.-T., Kim, J.-H., Hikichi, T., Wakayama, S., Kishigami, S., Mizutani, E., and Wakayama, T. (2009). The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice. Reproduction 138, 309-317.
    • (2009) Reproduction , vol.138 , pp. 309-317
    • Van Thuan, N.1    Bui, H.-T.2    Kim, J.-H.3    Hikichi, T.4    Wakayama, S.5    Kishigami, S.6    Mizutani, E.7    Wakayama, T.8
  • 48
    • 77649335496 scopus 로고    scopus 로고
    • How to improve the success rate of mouse cloning technology
    • Van Thuan, N., Kishigami, S., and Wakayama, T. (2010). How to improve the success rate of mouse cloning technology. J. Reprod. Dev. 56, 20-30.
    • (2010) J. Reprod. Dev. , vol.56 , pp. 20-30
    • Van Thuan, N.1    Kishigami, S.2    Wakayama, T.3
  • 49
    • 67650564895 scopus 로고    scopus 로고
    • Transcription-independent heritability of induced histone modifications in themouse preimplantation embryo
    • VerMilyea, M.D., O'Neill, L.P., and Turner, B.M. (2009). Transcription-independent heritability of induced histone modifications in themouse preimplantation embryo. PLoSOne 4, e6086.
    • (2009) PLoSOne , vol.4 , pp. e6086
    • Vermilyea, M.D.1    O'Neill, L.P.2    Turner, B.M.3
  • 50
    • 80051481672 scopus 로고    scopus 로고
    • Improvement of mouse cloning using nuclear transfer-derived embryonic stemcells and/or histone deacetylase inhibitor
    • Wakayama, S., andWakayama, T. (2010). Improvement of mouse cloning using nuclear transfer-derived embryonic stemcells and/or histone deacetylase inhibitor. Int. J. Dev.Biol. 54, 1641-1648.
    • (2010) Int. J. Dev.Biol. , vol.54 , pp. 1641-1648
    • Wakayama, S.1    Wakayama, T.2
  • 51
    • 36549105085 scopus 로고    scopus 로고
    • Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos
    • Wang, F., Kou, Z., Zhang, Y., and Gao, S. (2007). Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos. Biol. Reprod. 77, 1007-1016.
    • (2007) Biol. Reprod. , vol.77 , pp. 1007-1016
    • Wang, F.1    Kou, Z.2    Zhang, Y.3    Gao, S.4
  • 52
    • 84859511745 scopus 로고    scopus 로고
    • Valproic acid improves the in vitro development competence of bovine somatic cell nuclear transfer embryos
    • Xu, W., Wang, Y., Li, Y., Wang, L., Xiong, X., Su, J., and Zhang, Y. (2012). Valproic acid improves the in vitro development competence of bovine somatic cell nuclear transfer embryos. Cell. Reprogram. 14, 138-145.
    • (2012) Cell. Reprogram. , vol.14 , pp. 138-145
    • Xu, W.1    Wang, Y.2    Li, Y.3    Wang, L.4    Xiong, X.5    Su, J.6    Zhang, Y.7
  • 53
    • 33847275530 scopus 로고    scopus 로고
    • Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning
    • Yang, X., Smith, S.L., Tian, X.C., Lewin, H.A., Renard, J.-P., and Wakayama, T. (2007). Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat. Genet. 39, 295-302.
    • (2007) Nat. Genet. , vol.39 , pp. 295-302
    • Yang, X.1    Smith, S.L.2    Tian, X.C.3    Lewin, H.A.4    Renard, J.-P.5    Wakayama, T.6


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.