Skip to main content

Advertisement

SpringerLink
Log in

Mechanism of ABA signal transduction: Agricultural highlights for improving drought tolerance

  • Review Article
  • Published:
Journal of Plant Biology Aims and scope Submit manuscript

Abstract

Recent progress has been made in understanding the mechanism of ABA signal transduction based on identification of novel genetic components as well as decoding of signaling networks. This has resulted in a wide range of genetic targets for manipulation of crop genomes to obtain drought-tolerant traits. Early events in ABA signaling involve PYR/PYL/RCAR ABA receptors as well as two phosphatase/kinase enzyme pairs, PP2Cs and SnRK2s, with opposite functions. In the end, a number of transcription factors under the control of SnRK2s activate the ABA-dependent gene expression resulting in drought-resistant responses. Due to the evolutionary conservation of ABA signaling and plant drought stress responses in vascular plants, genes identified as major ABA signaling components in Arabidopsis can be used as targets for genetic manipulation of profitable crop species. Therefore, modulation of genes or application of small compounds that specifically function in ABA signal transduction might offer a unique pathway to addressing the global demand aims for the drought- or water deficiency-resistant crop lines without growth penalty.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amir Hossain M, Lee Y, Cho JI, Ahn CH, Lee SK, Jeon JS, Kang H, Lee CH, An G, Park PB (2010) The bZIP transcription factor OsABF1 is an ABA responsive element binding factor that enhances abiotic stress signaling in rice. Plant Mol Biol 72:557–566

    Article  CAS  PubMed  Google Scholar 

  • Antoni R, Rodriguez L, Gonzalez-Guzman M, Pizzio GA, Rodriguez PL (2011) News on ABA transport, protein degradation, and ABFs/WRKYs in ABA signaling. Curr Opin Plant Biol 14:547–553

    Article  CAS  PubMed  Google Scholar 

  • Ashraf M (2010) Inducing drought tolerance in plants: recent advances. Biotechnol Adv 28:169–183

    Article  CAS  PubMed  Google Scholar 

  • Brandt B, Brodsky DE, Xue S, Negi J, Iba K, Kangasjarvi J, Ghassemian M, Stephan AB, Hu H, Schroeder JI (2012) Reconstitution of abscisic acid activation of SLAC1 anion channel by CPK6 and OST1 kinases and branched ABI1 PP2C phosphatase action. Proc Natl Acad Sci USA 109:10593–10598

    Article  CAS  PubMed  Google Scholar 

  • Cao M, Liu X, Zhang Y, Xue X, Zhou XE, Melcher K, Gao P, Wang F, Zeng L, Zhao Y, Deng P, Zhong D, Zhu JK, Xu HE, Xu Y (2013) An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants. Cell Res 23:1043–1054

    Article  CAS  PubMed  Google Scholar 

  • Chae MJ, Lee JS, Nam MH, Cho K, Hong JY, Yi SA, Suh SC, Yoon IS (2007) A rice dehydration-inducible SNF1-related protein kinase 2 phosphorylates an abscisic acid responsive element-binding factor and associates with ABA signaling. Plant Mol Biol 63:151–169

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Chen W, Zhou J, He H, Chen L, Deng XW (2012) Basic leucine zipper transcription factor OsbZIP16 positively regulates drought resistance in rice. Plant Sci 193–194:8–17

    Article  PubMed  Google Scholar 

  • Cutler SR, Rodriguez PL, Finkelstein RR, Abrams SR (2010) Abscisic acid: emergence of a core signaling network. Annu Rev Plant Biol 61:651–679

    Article  CAS  PubMed  Google Scholar 

  • Ding H, Zhang A, Wang J, Lu R, Zhang H, Zhang J, Jiang M (2009) Identity of an ABA-activated 46 kDa mitogen-activated protein kinase from Zea mays leaves: partial purification, identification and characterization. Planta 230:239–251

    Article  CAS  PubMed  Google Scholar 

  • Ding Y, Cao J, Ni L, Zhu Y, Zhang A, Tan M, Jiang M (2013) ZmCPK11 is involved in abscisic acid-induced antioxidant defence and functions upstream of ZmMPK5 in abscisic acid signalling in maize. J Exp Bot 64:871–884

    Article  CAS  PubMed  Google Scholar 

  • Fujii H, Chinnusamy V, Rodrigues A, Rubio S, Antoni R, Park SY, Cutler SR, Sheen J, Rodriguez PL, Zhu JK (2009) In vitro reconstitution of an abscisic acid signalling pathway. Nature 462:660–664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fujii H, Zhu JK (2009) Arabidopsis mutant deficient in 3 abscisic acid-activated protein kinases reveals critical roles in growth, reproduction, and stress. Proc Natl Acad Sci USA 106:8380–8385

    Article  CAS  PubMed  Google Scholar 

  • Fujita Y, Fujita M, Shinozaki K, Yamaguchi-Shinozaki K (2011) ABA-mediated transcriptional regulation in response to osmotic stress in plants. J Plant Res 124:509–525

    Article  CAS  PubMed  Google Scholar 

  • Fujita Y, Nakashima K, Yoshida T, Katagiri T, Kidokoro S, Kanamori N, Umezawa T, Fujita M, Maruyama K, Ishiyama K, Kobayashi M, Nakasone S, Yamada K, Ito T, Shinozaki K, Yamaguchi-Shinozaki K (2009) Three SnRK2 protein kinases are the main positive regulators of abscisic acid signaling in response to water stress in Arabidopsis. Plant Cell Physiol 50:2123–2132

    Article  CAS  PubMed  Google Scholar 

  • Gao SQ, Chen M, Xu ZS, Zhao CP, Li L, Xu HJ, Tang YM, Zhao X, Ma YZ (2011) The soybean GmbZIP1 transcription factor enhances multiple abiotic stress tolerances in transgenic plants. Plant Mol Biol 75:537–553

    Article  CAS  PubMed  Google Scholar 

  • Geiger D, Scherzer S, Mumm P, Marten I, Ache P, Matschi S, Liese A, Wellmann C, Al-Rasheid KA, Grill E, Romeis T, Hedrich R (2010) Guard cell anion channel SLAC1 is regulated by CDPK protein kinases with distinct Ca2+ affinities. Proc Natl Acad Sci USA 107:8023–8028

    Article  CAS  PubMed  Google Scholar 

  • Geiger D, Scherzer S, Mumm P, Stange A, Marten I, Bauer H, Ache P, Matschi S, Liese A, Al-Rasheid KA, Romeis T, Hedrich R (2009) Activity of guard cell anion channel SLAC1 is controlled by drought-stress signaling kinase-phosphatase pair. Proc Natl Acad Sci USA 106:21425–21430

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Guzman M, Pizzio GA, Antoni R, Vera-Sirera F, Merilo E, Bassel GW, Fernandez MA, Holdsworth MJ, Perez-Amador MA, Kollist H, Rodriguez PL (2012) Arabidopsis PYR/PYL/RCAR receptors play a major role in quantitative regulation of stomatal aperture and transcriptional response to abscisic acid. Plant Cell 24:2483–2496

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hadiarto T, Tran LS (2011) Progress studies of drought-responsive genes in rice. Plant Cell Rep 30:297–310

    Article  CAS  PubMed  Google Scholar 

  • Han SK, Wagner D (2013) Role of chromatin in water stress responses in plants. J Exp Bot: doi: 10.1093/jxb/ert403

    Google Scholar 

  • Hu H, Xiong L (2014) Genetic engineering and breeding of droughtresistant crops. Annu Rev Plant Biol 65:3.1–3.27

    Google Scholar 

  • Imes D, Mumm P, Bohm J, Al-Rasheid KA, Marten I, Geiger D, Hedrich R (2013) Open stomata 1 (OST1) kinase controls Rtype anion channel QUAC1 in Arabidopsis guard cells. Plant J 74:372–382

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Hwang H, Hong JW, Lee YN, Ahn IP, Yoon IS, Yoo SD, Lee S, Lee SC, Kim BG (2012) A rice orthologue of the ABA receptor, OsPYL/RCAR5, is a positive regulator of the ABA signal transduction pathway in seed germination and early seedling growth. J Exp Bot 63:1013–1024

    Article  CAS  PubMed  Google Scholar 

  • Kim TH, Bohmer M, Hu H, Nishimura N, Schroeder JI (2010) Guard cell signal transduction network: advances in understanding abscisic acid, CO2, and Ca2+ signaling. Annu Rev Plant Biol 61:561–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kobayashi Y, Yamamoto S, Minami H, Kagaya Y, Hattori T (2004) Differential activation of the rice sucrose nonfermenting1-related protein kinase2 family by hyperosmotic stress and abscisic acid. Plant Cell 16:1163–1177

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kusumi K, Hirotsuka S, Kumamaru T, Iba K (2012) Increased leaf photosynthesis caused by elevated stomatal conductance in a rice mutant deficient in SLAC1, a guard cell anion channel protein. J Exp Bot 63:5635–5644

    Article  CAS  PubMed  Google Scholar 

  • Lawlor DW (2013) Genetic engineering to improve plant performance under drought: physiological evaluation of achievements, limitations, and possibilities. J Exp Bot 64:83–108

    Article  CAS  PubMed  Google Scholar 

  • Lee SC, Lan W, Buchanan BB, Luan S (2009) A protein kinasephosphatase pair interacts with an ion channel to regulate ABA signaling in plant guard cells. Proc Natl Acad Sci USA 106:21419–21424

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Mao B, Ou S, Wang W, Liu L, Wu Y, Chu C, Wang X (2014) OsbZIP71, a bZIP transcription factor, confers salinity and drought tolerance in rice. Plant Mol Biol 84:19–36

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Hu X, Song J, Zong X, Li D (2009) Over-expression of a Zea mays L. protein phosphatase 2C gene (ZmPP2C) in Arabidopsis thaliana decreases tolerance to salt and drought. J Plant Physiol 166:531–542

    Article  CAS  PubMed  Google Scholar 

  • Lu G, Gao C, Zheng X, Han B (2009) Identification of OsbZIP72 as a positive regulator of ABA response and drought tolerance in rice. Planta 229:605–615

    Article  CAS  PubMed  Google Scholar 

  • Luo X, Bai X, Sun X, Zhu D, Liu B, Ji W, Cai H, Cao L, Wu J, Hu M, Liu X, Tang L, Zhu Y (2013) Expression of wild soybean WRKY20 in Arabidopsis enhances drought tolerance and regulates ABA signalling. J Exp Bot 64:2155–2169

    Article  CAS  PubMed  Google Scholar 

  • Ma Y, Szostkiewicz I, Korte A, Moes D, Yang Y, Christmann A, Grill E (2009) Regulators of PP2C phosphatase activity function as abscisic acid sensors. Science 324:1064–1068

    CAS  PubMed  Google Scholar 

  • Manmathan H, Shaner D, Snelling J, Tisserat N, Lapitan N (2013) Virus-induced gene silencing of Arabidopsis thaliana gene homologues in wheat identifies genes conferring improved drought tolerance. J Exp Bot 64:1381–1392

    Article  CAS  PubMed  Google Scholar 

  • Mao X, Zhang H, Tian S, Chang X, Jing R (2010) TaSnRK2.4, an SNF1-type serine/threonine protein kinase of wheat (Triticum aestivum L.), confers enhanced multistress tolerance in Arabidopsis. J Exp Bot 61:683–696

    Article  CAS  PubMed  Google Scholar 

  • Melcher K, Ng LM, Zhou XE, Soon FF, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Peterson FC, Jensen DR, Yong EL, Volkman BF, Cutler SR, Zhu JK, Xu HE (2009) A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature 462:602–608

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meyer S, Mumm P, Imes D, Endler A, Weder B, Al-Rasheid KA, Geiger D, Marten I, Martinoia E, Hedrich R (2010) AtALMT12 represents an R-type anion channel required for stomatal movement in Arabidopsis guard cells. Plant J 63:1054–1062

    Article  CAS  PubMed  Google Scholar 

  • Miyazono K, Miyakawa T, Sawano Y, Kubota K, Kang HJ, Asano A, Miyauchi Y, Takahashi M, Zhi Y, Fujita Y, Yoshida T, Kodaira KS, Yamaguchi-Shinozaki K, Tanokura M (2009) Structural basis of abscisic acid signalling. Nature 462:609–614

    Article  CAS  PubMed  Google Scholar 

  • Nakashima K, Takasaki H, Mizoi J, Shinozaki K, Yamaguchi-Shinozaki K (2012) NAC transcription factors in plant abiotic stress responses. Biochim Biophys Acta 1819:97–103

    Article  CAS  PubMed  Google Scholar 

  • Nakashima K, Tran LS, Van Nguyen D, Fujita M, Maruyama K, Todaka D, Ito Y, Hayashi N, Shinozaki K, Yamaguchi-Shinozaki K (2007) Functional analysis of a NAC-type transcription factor OsNAC6 involved in abiotic and biotic stress-responsive gene expression in rice. Plant J 51:617–630

    Article  CAS  PubMed  Google Scholar 

  • Ng LM, Soon FF, Zhou XE, West GM, Kovach A, Suino-Powell KM, Chalmers MJ, Li J, Yong EL, Zhu JK, Griffin PR, Melcher K, Xu HE (2011) Structural basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases. Proc Natl Acad Sci USA 108:21259–21264

    Article  CAS  PubMed  Google Scholar 

  • Ni Z, Hu Z, Jiang Q, Zhang H (2013) GmNFYA3, a target gene of miR169, is a positive regulator of plant tolerance to drought stress. Plant Mol Biol 82:113–129

    Article  CAS  PubMed  Google Scholar 

  • Nishimura N, Hitomi K, Arvai AS, Rambo RP, Hitomi C, Cutler SR, Schroeder JI, Getzoff ED (2009) Structural mechanism of abscisic acid binding and signaling by dimeric PYR1. Science 326:1373–1379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nishimura N, Sarkeshik A, Nito K, Park SY, Wang A, Carvalho PC, Lee S, Caddell DF, Cutler SR, Chory J, Yates JR, Schroeder JI (2010) PYR/PYL/RCAR family members are major in-vivo ABI1 protein phosphatase 2C-interacting proteins in Arabidopsis. Plant J 61:290–299

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Niu CF, Wei W, Zhou QY, Tian AG, Hao YJ, Zhang WK, Ma B, Lin Q, Zhang ZB, Zhang JS, Chen SY (2012) Wheat WRKY genes TaWRKY2 and TaWRKY19 regulate abiotic stress tolerance in transgenic Arabidopsis plants. Plant Cell Environ 35:1156–1170

    Article  CAS  PubMed  Google Scholar 

  • Okamoto M, Peterson FC, Defries A, Park SY, Endo A, Nambara E, Volkman BF, Cutler SR (2013) Activation of dimeric ABA receptors elicits guard cell closure, ABA-regulated gene expression, and drought tolerance. Proc Natl Acad Sci USA 110:12132–12137

    Article  CAS  PubMed  Google Scholar 

  • Park SY, Fung P, Nishimura N, Jensen DR, Fujii H, Zhao Y, Lumba S, Santiago J, Rodrigues A, Chow TF, Alfred SE, Bonetta D, Finkelstein R, Provart NJ, Desveaux D, Rodriguez PL, McCourt P, Zhu JK, Schroeder JI, Volkman BF, Cutler SR (2009) Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins. Science 324:1068–1071

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pizzio GA, Rodriguez L, Antoni R, Gonzalez-Guzman M, Yunta C, Merilo E, Kollist H, Albert A, Rodriguez PL (2013) The PYL4 A194T mutant uncovers a key role of PYR1-LIKE4/PROTEIN PHOSPHATASE 2CA interaction for abscisic acid signaling and plant drought resistance. Plant Physiol 163:441–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roychoudhury A, Paul S, Basu S (2013) Cross-talk between abscisic acid-dependent and abscisic acid-independent pathways during abiotic stress. Plant Cell Rep 32:985–1006

    Article  CAS  PubMed  Google Scholar 

  • Rushton DL, Tripathi P, Rabara RC, Lin J, Ringler P, Boken AK, Langum TJ, Smidt L, Boomsma DD, Emme NJ, Chen X, Finer JJ, Shen QJ, Rushton PJ (2012) WRKY transcription factors: key components in abscisic acid signalling. Plant Biotechnol J 10:2–11

    Article  CAS  PubMed  Google Scholar 

  • Santiago J, Dupeux F, Round A, Antoni R, Park SY, Jamin M, Cutler SR, Rodriguez PL, Marquez JA (2009) The abscisic acid receptor PYR1 in complex with abscisic acid. Nature 462:665–668

    Article  CAS  PubMed  Google Scholar 

  • Song SY, Chen Y, Chen J, Dai XY, Zhang WH (2011) Physiological mechanisms underlying OsNAC5-dependent tolerance of rice plants to abiotic stress. Planta 234:331–345

    Article  CAS  PubMed  Google Scholar 

  • Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MH, Suino-Powell KM, He Y, Xu Y, Chalmers MJ, Brunzelle JS, Zhang H, Yang H, Jiang H, Li J, Yong EL, Cutler S, Zhu JK, Griffin PR, Melcher K, Xu HE (2012) Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science 335:85–88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sunkar R, Chinnusamy V, Zhu J, Zhu JK (2007) Small RNAs as big players in plant abiotic stress responses and nutrient deprivation. Trends Plant Sci 12:301–309

    Article  CAS  PubMed  Google Scholar 

  • Takasaki H, Maruyama K, Kidokoro S, Ito Y, Fujita Y, Shinozaki K, Yamaguchi-Shinozaki K, Nakashima K (2010) The abiotic stress-responsive NAC-type transcription factor OsNAC5 regulates stress-inducible genes and stress tolerance in rice. Mol Genet Genomics 284:173–183

    Article  CAS  PubMed  Google Scholar 

  • Tang N, Zhang H, Li X, Xiao J, Xiong L (2012a) Constitutive activation of transcription factor OsbZIP46 improves drought tolerance in rice. Plant Physiol 158:1755–1768

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tang Y, Liu M, Gao S, Zhang Z, Zhao X, Zhao C, Zhang F, Chen X (2012b) Molecular characterization of novel TaNAC genes in wheat and overexpression of TaNAC2a confers drought tolerance in tobacco. Physiol Plant 144:210–224

    Article  CAS  PubMed  Google Scholar 

  • Tao Z, Kou Y, Liu H, Li X, Xiao J, Wang S (2011) OsWRKY45 alleles play different roles in abscisic acid signalling and salt stress tolerance but similar roles in drought and cold tolerance in rice. J Exp Bot 62:4863–4874

    Article  CAS  PubMed  Google Scholar 

  • Tao Z, Liu H, Qiu D, Zhou Y, Li X, Xu C, Wang S (2009) A pair of allelic WRKY genes play opposite roles in rice-bacteria interactions. Plant Physiol 151:936–948

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vilela B, Moreno-Cortes A, Rabissi A, Leung J, Pages M, Lumbreras V (2013) The maize OST1 kinase homolog phosphorylates and regulates the maize SNAC1-type transcription factor. PLoS One 8:e58105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang M, Yuan F, Hao H, Zhang Y, Zhao H, Guo A, Hu J, Zhou X, Xie CG (2013) BolOST1, an ortholog of Open Stomata 1 with alternative splicing products in Brassica oleracea, positively modulates drought responses in plants. Biochem Biophys Res Commun 442:214–220

    Article  CAS  PubMed  Google Scholar 

  • Xiang Y, Tang N, Du H, Ye H, Xiong L (2008) Characterization of OsbZIP23 as a key player of the basic leucine zipper transcription factor family for conferring abscisic acid sensitivity and salinity and drought tolerance in rice. Plant Physiol 148:1938–1952

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguchi-Shinozaki K, Shinozaki K (2005) Organization of cisacting regulatory elements in osmotic- and cold-stress-responsive promoters. Trends Plant Sci 10:88–94

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Ji W, Gao P, Li Y, Cai H, Bai X, Chen Q, Zhu Y (2012) GsAPK, an ABA-activated and calcium-independent SnRK2-type kinase from G. soja, mediates the regulation of plant tolerance to salinity and ABA stress. PLoS One 7:e33838

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yin P, Fan H, Hao Q, Yuan X, Wu D, Pang Y, Yan C, Li W, Wang J, Yan N (2009) Structural insights into the mechanism of abscisic acid signaling by PYL proteins. Nat Struct Mol Biol 16:1230–1236

    Article  CAS  PubMed  Google Scholar 

  • Ying S, Zhang DF, Fu J, Shi YS, Song YC, Wang TY, Li Y (2012) Cloning and characterization of a maize bZIP transcription factor, ZmbZIP72, confers drought and salt tolerance in transgenic Arabidopsis. Planta 235:253–266

    Article  CAS  PubMed  Google Scholar 

  • Yuan F, Wang M, Hao H, Zhang Y, Zhao H, Guo A, Xu H, Zhou X, Xie CG (2013) Negative regulation of abscisic acid signaling by the Brassica oleracea ABI1 ortholog. Biochem Biophys Res Commun 442:202–208

    Article  CAS  PubMed  Google Scholar 

  • Zeevaart JA (1980) Changes in the levels of abscisic acid and its metabolites in excised leaf blades of Xanthium strumarium during and after water stress. Plant Physiol 66:672–678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang H, Mao X, Wang C, Jing R (2010) Overexpression of a common wheat gene TaSnRK2.8 enhances tolerance to drought, salt and low temperature in Arabidopsis. PLoS One 5:e16041

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou X, Yuan F, Wang M, Guo A, Zhang Y, Xie CG (2013) Molecular characterization of an ABA insensitive 5 orthologue in Brassica oleracea. Biochem Biophys Res Commun 430:1140–1146

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Prepharm-Med/Health Functional Biomaterials, College of Natural Sciences, Duksung Women’s University, Seoul, 132-714, Korea

    Tae-Houn Kim

Authors
  1. Tae-Houn Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tae-Houn Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, TH. Mechanism of ABA signal transduction: Agricultural highlights for improving drought tolerance. J. Plant Biol. 57, 1–8 (2014). https://doi.org/10.1007/s12374-014-0901-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12374-014-0901-8

Keywords

Search

Navigation