Skip to main content

Advertisement

SpringerLink
Log in

Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes

  • Original Paper
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

Previously, we found that the Graffi murine leukemia virus (MuLV) is able to induce a wide spectrum of hematologic malignancies in vivo. Using high-density oligonucleotide microarrays, we established the gene expression profiles of several of these malignancies, thereby specifically focusing on genes deregulated in the lymphoid sub-types. We observed over-expression of a variety of genes, including Arntl2, Bfsp2, Gfra2, Gpm6a, Gpm6b, Nln, Fbln1, Bmp7, Etv5 and Celsr1 and, in addition, provided evidence that Fmn2 and Parm-1 may act as novel oncogenes. In the present study, we assessed the expression patterns of eight selected human homologs of these genes in primary human B-cell malignancies, and explored the putative oncogenic potential of GPM6A and GPM6B.

Methods

The gene expression levels of the selected human homologs were tested in human B-cell malignancies by semi-quantitative RT-PCR. The protein expression profiles of human GPM6A and GPM6B were analyzed by Western blotting. The localization and the effect of GPM6A and GPM6B on the cytoskeleton were determined using confocal and indirect immunofluorescence microscopy. To confirm the oncogenic potential of GPM6A and GPM6B, classical colony formation assays in soft agar and focus forming assays were used. The effects of these proteins on the cell cycle were assessed by flow cytometry analysis.

Results

Using semi-quantitative RT-PCR, we found that most of the primary B-cell malignancies assessed showed altered expression patterns of the genes tested, including GPM6A and GPM6B. Using confocal microscopy, we found that the GPM6A protein (isoform 3) exhibits a punctate cytoplasmic localization and that the GPM6B protein (isoform 4) exhibits a peri-nuclear and punctate cytoplasmic localization. Interestingly, we found that exogenous over-expression of both proteins in NIH/3T3 cells alters the actin and microtubule networks and induces the formation of long filopodia-like protrusions. Additionally, we found that these over-expressing NIH/3T3 cells exhibit anchorage-independent growth and enhanced proliferation rates. Cellular transformation (i.e., loss of contact inhibition) was, however, only observed after exogenous over-expression of GPM6B.

Conclusions

Our results indicate that several human homologs of the genes found to be deregulated in Graffi MuLV experimental mouse models may serve as candidate biomarkers for human B-cell malignancies. In addition, we found that GPM6A and GPM6B may act as novel oncogenes in the development of these malignancies.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. A. Graffi, Chloroleukemia of mice. Ann. N. Y. Acad. Sci. 68, 540–558 (1957)

    Article  CAS  PubMed  Google Scholar 

  2. V. Voisin, C. Barat, T. Hoang, E. Rassart, Novel insights into the pathogenesis of the Graffi murine leukemia retrovirus. J. Virol. 80, 4026–4037 (2006)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. C. Denicourt, E. Edouard, E. Rassart, Oncogene activation in myeloid leukemias by Graffi murine leukemia virus proviral integration. J. Virol. 73, 4439–4442 (1999)

    CAS  PubMed Central  PubMed  Google Scholar 

  4. C. Denicourt, C.A. Kozak, E. Rassart, Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing. J. Virol. 77, 37–44 (2003)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. C. Denicourt, P. Legault, F.A. McNabb, E. Rassart, Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization. Oncogene 27, 1253–1262 (2008)

    Article  CAS  PubMed  Google Scholar 

  6. C. Charfi, V. Voisin, L.C. Levros Jr., E. Edouard, E. Rassart, Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene. Blood 117, 1899–1910 (2011)

    Article  CAS  PubMed  Google Scholar 

  7. C. Charfi, L.C. Levros Jr., E. Edouard, E. Rassart, Characterization and identification of PARM-1 as a new potential oncogene. Mol. Cancer 12, 84 (2013)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. X. Castells, J.J. Acebes, S. Boluda, A. Moreno-Torres, J. Pujol, M. Julia-Sape, A.P. Candiota, J. Arino, A. Barcelo, C. Arus, Development of a predictor for human brain tumors based on gene expression values obtained from two types of microarray technologies. OMICS 14, 157–164 (2010)

    Article  CAS  PubMed  Google Scholar 

  9. P. Urban, M. Bilecova-Rabajdova, Z. Stefekova, A. Ostro, M. Marekova, Overview of potential oncomarkers for detection of early stages of ovarian cancer. Klin. Onkol. 24, 106–111 (2011)

    CAS  PubMed  Google Scholar 

  10. S. Landais, S. Landry, P. Legault, E. Rassart, Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia. Cancer Res. 67, 5699–5707 (2007)

    Article  CAS  PubMed  Google Scholar 

  11. M. Ru, C. Shustik, E. Rassart, Graffi murine leukemia virus: molecular cloning and characterization of the myeloid leukemia-inducing agent. J. Virol. 67, 4722–4731 (1993)

    CAS  PubMed Central  PubMed  Google Scholar 

  12. E. Edouard, C. Charfi, V. Voisin, C. Denicourt, C. Barat, E. Rassart, The Graffi murine leukemia virus: a multipotent retrovirus ideal for the study and characterization of lymphoid and non lymphoid leukemias. Transw. Res. Netw. 8, 23–47 (2012)

    Google Scholar 

  13. V. Voisin, P. Legault, D.P. Ospina, Y. Ben-David, E. Rassart, Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus. BMC Med. Genomics 3, 2 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  14. F. Sievers, A. Wilm, D. Dineen, T.J. Gibson, K. Karplus, W. Li, R. Lopez, H. McWilliam, M. Remmert, J. Soding, J.D. Thompson, D.G. Higgins, Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011)

    Article  PubMed Central  PubMed  Google Scholar 

  15. K.C. Chou, H.B. Shen, Signal-CF: a subsite-coupled and window-fusing approach for predicting signal peptides. Biochem. Biophys. Res. Commun. 357, 633–640 (2007)

    Article  CAS  PubMed  Google Scholar 

  16. N.H. Colburn, W.F. Bruegge, J.R. Bates, R.H. Gray, J.D. Rossen, W.H. Kelsey, T. Shimada, Correlation of anchorage-independent growth with tumorigenicity of chemically transformed mouse epidermal cells. Cancer Res. 38, 624–634 (1978)

    CAS  PubMed  Google Scholar 

  17. V.H. Freedman, S.I. Shin, Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell 3, 355–359 (1974)

    Article  CAS  PubMed  Google Scholar 

  18. S.I. Shin, V.H. Freedman, R. Risser, R. Pollack, Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc. Natl. Acad. Sci. U. S. A. 72, 4435–4439 (1975)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. C. Charfi, E. Edouard, E. Rassart, Lymphoid leukemias induced by the murine retrovirus Graffi. http://www.biomed.uqam.ca/rassart/microarray2.html. Accessed 14 November 2013

  20. M. Ikeda, W. Yu, M. Hirai, T. Ebisawa, S. Honma, K. Yoshimura, K.I. Honma, M. Nomura, cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2: its mRNA expression, subcellular distribution, and chromosomal localization. Biochem. Biophys. Res. Commun. 275, 493–502 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. S. Jones, An overview of the basic helix-loop-helix proteins. Genome Biol. 5, 226 (2004)

    Article  PubMed Central  PubMed  Google Scholar 

  22. Y. Yasuniwa, H. Izumi, K.Y. Wang, S. Shimajiri, Y. Sasaguri, K. Kawai, H. Kasai, T. Shimada, K. Miyake, E. Kashiwagi, G. Hirano, A. Kidani, M. Akiyama, B. Han, Y. Wu, I. Ieiri, S. Higuchi, K. Kohno, Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway. PLoS ONE 5, e15330 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. G. Mazzoccoli, V. Pazienza, A. Panza, M.R. Valvano, G. Benegiamo, M. Vinciguerra, A. Andriulli, A. Piepoli, ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer. J. Cancer Res. Clin. Oncol. 138, 501–511 (2012)

    Article  CAS  PubMed  Google Scholar 

  24. S.D. Georgatos, F. Gounari, S. Remington, The beaded intermediate filaments and their potential functions in eye lens. BioEssays 16, 413–418 (1994)

    Article  CAS  PubMed  Google Scholar 

  25. M.D. Perng, Q. Zhang, R.A. Quinlan, Insights into the beaded filament of the eye lens. Exp. Cell Res. 313, 2180–2188 (2007)

    Article  CAS  PubMed  Google Scholar 

  26. M.A. Aldahmesh, A.O. Khan, J. Mohamed, F.S. Alkuraya, Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. Genet. Med. 13, 978–981 (2011)

    Article  CAS  PubMed  Google Scholar 

  27. G. Wu, L. Zhou, L. Khidr, X.E. Guo, W. Kim, Y.M. Lee, T. Krasieva, P.L. Chen, A novel role of the chromokinesin Kif4A in DNA damage response. Cell Cycle 7, 2013–2020 (2008)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Y. Kurasawa, W.C. Earnshaw, Y. Mochizuki, N. Dohmae, K. Todokoro, Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 23, 3237–3248 (2004)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. M. Mazumdar, J.H. Lee, K. Sengupta, T. Ried, S. Rane, T. Misteli, Tumor formation via loss of a molecular motor protein. Curr. Biol. 16, 1559–1564 (2006)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Y.S. Kim, J.D. Hwan, S. Bae, D.H. Bae, W.A. Shick, Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma. BMC Cancer 10, 576 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. L.L. Yates, C. Schnatwinkel, J.N. Murdoch, D. Bogani, C.J. Formstone, S. Townsend, A. Greenfield, L.A. Niswander, C.H. Dean, The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum. Mol. Genet. 19, 2251–2267 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. M. Katoh, Comparative integromics on non-canonical WNT or planar cell polarity signaling molecules: transcriptional mechanism of PTK7 in colorectal cancer and that of SEMA6A in undifferentiated ES cells. Int. J. Mol. Med. 20, 405–409 (2007)

    CAS  PubMed  Google Scholar 

  33. C. Korz, A. Pscherer, A. Benner, D. Mertens, C. Schaffner, E. Leupolt, H. Dohner, S. Stilgenbauer, P. Lichter, Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosis-associated genes. Blood 99, 4554–4561 (2002)

    Article  CAS  PubMed  Google Scholar 

  34. A.W. Fjorback, H.K. Muller, O. Wiborg, Membrane glycoprotein M6B interacts with the human serotonin transporter. J. Mol. Neurosci. 37, 191–200 (2009)

    Article  CAS  PubMed  Google Scholar 

  35. S. Olinsky, B.T. Loop, A. DeKosky, B. Ripepi, W. Weng, J. Cummins, S.L. Wenger, Y. Yan, C. Lagenaur, V. Narayanan, Chromosomal mapping of the human M6 genes. Genomics 33, 532–536 (1996)

    Article  CAS  PubMed  Google Scholar 

  36. N.L. Nadon, S. Miller, K. Draeger, M. Salvaggio, Myelin proteolipid DM20: evidence for function independent of myelination. Int. J. Dev. Neurosci. 15, 285–293 (1997)

    Article  CAS  PubMed  Google Scholar 

  37. X. Castells, J.M. Garcia-Gomez, A. Navarro, J.J. Acebes, O. Godino, S. Boluda, A. Barcelo, M. Robles, J. Arino, C. Arus, Automated brain tumor biopsy prediction using single-labeling cDNA microarrays-based gene expression profiling. Diagn. Mol. Pathol. 18, 206–218 (2009)

    Article  CAS  PubMed  Google Scholar 

  38. Y. Yan, C. Lagenaur, V. Narayanan, Molecular cloning of M6: identification of a PLP/DM20 gene family. Neuron 11, 423–431 (1993)

    Article  CAS  PubMed  Google Scholar 

  39. H. Werner, L. Dimou, M. Klugmann, S. Pfeiffer, K.A. Nave, Multiple splice isoforms of proteolipid M6B in neurons and oligodendrocytes. Mol. Cell. Neurosci. 18, 593–605 (2001)

    Article  CAS  PubMed  Google Scholar 

  40. J.L. Popot, D. Pham Dinh, A. Dautigny, Major myelin proteolipid: the 4-alpha-helix topology. J. Membr. Biol. 120, 233–246 (1991)

    Article  CAS  PubMed  Google Scholar 

  41. T. Weimbs, W. Stoffel, Proteolipid protein (PLP) of CNS myelin: positions of free, disulfide-bonded, and fatty acid thioester-linked cysteine residues and implications for the membrane topology of PLP. Biochemistry 31, 12289–12296 (1992)

    Article  CAS  PubMed  Google Scholar 

  42. A. Gow, A. Gragerov, A. Gard, D.R. Colman, R.A. Lazzarini, Conservation of topology, but not conformation, of the proteolipid proteins of the myelin sheath. J. Neurosci. 17, 181–189 (1997)

    CAS  PubMed  Google Scholar 

  43. A.M. Schneider, I.R. Griffiths, C. Readhead, K.A. Nave, Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein. Proc. Natl. Acad. Sci. U. S. A. 92, 4447–4451 (1995)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. E. Swanton, A. Holland, S. High, P. Woodman, Disease-associated mutations cause premature oligomerization of myelin proteolipid protein in the endoplasmic reticulum. Proc. Natl. Acad. Sci. U. S. A. 102, 4342–4347 (2005)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. S. Yang, W. Wang, C. Lei, Q. Liu, F. Xu, X. Xing, H. Chen, J. Liu, S. Wu, M. Wang, Localization and characterization of rat transmembrane protein 225 specifically expressed in testis. DNA Cell Biol. 30, 9–16 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. M. Namiki, M. Kitamura, E. Buczko, M.L. Dufau, Rat testis P-450(17)alpha cDNA: the deduced amino acid sequence, expression and secondary structural configuration. Biochem. Biophys. Res. Commun. 157, 705–712 (1988)

    Article  CAS  PubMed  Google Scholar 

  47. J. Haugstetter, T. Blicher, L. Ellgaard, Identification and characterization of a novel thioredoxin-related transmembrane protein of the endoplasmic reticulum. J. Biol. Chem. 280, 8371–8380 (2005)

    Article  CAS  PubMed  Google Scholar 

  48. M. Schweneker, A.S. Bachmann, K. Moelling, JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Lett. 579, 1751–1758 (2005)

    Article  CAS  PubMed  Google Scholar 

  49. M. Wang, G. Luo, F. Li, S. Wu, J. Jiang, C. Huang, Isolation and characterization of a novel four-transmembrane protein PMP22CD specifically expressed in the testis. Int. J. Mol. Sci. 7, 425–437 (2006)

    Article  CAS  Google Scholar 

  50. H. Ohno, J. Stewart, M.C. Fournier, H. Bosshart, I. Rhee, S. Miyatake, T. Saito, A. Gallusser, T. Kirchhausen, J.S. Bonifacino, Interaction of tyrosine-based sorting signals with clathrin-associated proteins. Science 269, 1872–1875 (1995)

    Article  CAS  PubMed  Google Scholar 

  51. J.S. Bonifacino, E.C. Dell’Angelica, Molecular bases for the recognition of tyrosine-based sorting signals. J. Cell Biol. 145, 923–926 (1999)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. B.D. Trapp, A. Nishiyama, D. Cheng, W. Macklin, Molecular bases for the recognition of tyrosine-based sorting signals. J. Cell Biol. 137, 459–468 (1997)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. M.P. Sinoway, K. Kitagawa, S. Timsit, G.A. Hashim, D.R. Colman, Proteolipid protein interactions in transfectants: implications for myelin assembly. J. Neurosci. Res. 37, 551–562 (1994)

    Article  CAS  PubMed  Google Scholar 

  54. J. Alfonso, M.E. Fernandez, B. Cooper, G. Flugge, A.C. Frasch, The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation. Proc. Natl. Acad. Sci. U. S. A. 102, 17196–17201 (2005)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. B. Fuchsova, M.E. Fernandez, J. Alfonso, A.C. Frasch, Cysteine residues in the large extracellular loop (EC2) are essential for the function of the stress-regulated glycoprotein M6a. J. Biol. Chem. 284, 32075–32088 (2009)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. M.A. Brocco, M.E. Fernandez, A.C. Frasch, Filopodial protrusions induced by glycoprotein M6a exhibit high motility and aids synapse formation. Eur. J. Neurosci. 31, 195–202 (2010)

    Article  PubMed  Google Scholar 

  57. K.Y. Huang, G.D. Chen, C.H. Cheng, K.Y. Liao, C.C. Hung, G.D. Chang, P.P. Hwang, S.Y. Lin, M.C. Tsai, K.H. Khoo, M.T. Lee, C.J. Huang, Phosphorylation of the zebrafish M6Ab at serine 263 contributes to filopodium formation in PC12 cells and neurite outgrowth in zebrafish embryos. PLoS ONE 6, e26461 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. M.E. Fernandez, J. Alfonso, M.A. Brocco, A.C. Frasch, Conserved cellular function and stress-mediated regulation among members of the proteolipid protein family. J. Neurosci. Res. 88, 1298–1308 (2010)

    CAS  PubMed  Google Scholar 

  59. F. Xue, D.M. Janzen, D.A. Knecht, Contribution of filopodia to cell migration: a mechanical link between protrusion and contraction. Int. J. Cell Biol. 2010, 507821 (2010)

    PubMed Central  PubMed  Google Scholar 

  60. A. Arjonen, R. Kaukonen, J. Ivaska, Filopodia and adhesion in cancer cell motility. Cell Adhes. Migr. 5, 421–430 (2011)

    Article  Google Scholar 

  61. H. Li, S. Hou, X. Wu, S. Nandagopal, F. Lin, S. Kung, A.J. Marshall, The tandem PH domain-containing protein 2 (TAPP2) regulates chemokine-induced cytoskeletal reorganization and malignant B cell migration. PLoS ONE 8, e57809 (2013)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. C. Scielzo, M.T. Bertilaccio, G. Simonetti, A. Dagklis, E. ten Hacken, C. Fazi, M. Muzio, V. Caiolfa, D. Kitamura, U. Restuccia, A. Bachi, M. Rocchi, M. Ponzoni, P. Ghia, F. Caligaris-Cappio, HS1 has a central role in the trafficking and homing of leukemic B cells. Blood 116, 3537–3546 (2010)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Daniel Sinnet for providing the pediatric tumor samples, Bertrand Fournier for his help with the statistical analysis and Denis Flipo for his help with the confocal microscopy analyses. This work was supported by the Canadian Institutes of Health Research, grant MOP-37994 (ER). CC is a recipient of a studentship from the Tunisia Government and Fondation UQAM.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Centre BioMed, Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, QC, H3C-3P8, Canada

    Cyndia Charfi, Elsy Edouard & Eric Rassart

Authors
  1. Cyndia Charfi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elsy Edouard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric Rassart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Elsy Edouard or Eric Rassart.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource Fig. 1

Alignment of deduced amino acid sequences for GPM6A isoforms together and for GPM6B isoforms together. Alignment a of the 5 Homo sapiens isoforms of GPM6A (NP_005268 (isoform 1), NP_963885 (isoform 1), NP_001248376 (isoform 2), NP_963886 (isoform 3) and NP_001248377 (isoform 4)) and b of the 4 homosapiens isoforms of GPM6B protein (NP_001001995 (isoform 1), NP_005269 (isoform 3), NP_001001996 (isoform 2) and NP_001001994 (isoform 4)) using the Clustal Omega software. Stars indicate a perfect match between all aligned isoforms and dashed lines indicate gaps. (PDF 30 kb)

Online Resource Fig. 2

Alignment of GPM6A, GPM6B and DM20 proteins. The amino acid residues of GPM6A isoform 3, GPM6B isoform 4 and DM20 proteins were aligned in pairs to determine their identity percentage. a Alignment of GPM6A isoform 3 and GPM6B isoform 4. b Alignment of DM20 and GPM6A isoform 3. c Alignment of DM20 and GPM6B isoform 4. Boxes: N- and C- cytoplasmic tails, dotted lines: transmembrane domains, lines: extracellular loops, double lines: intracellular loop. (PDF 48 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Charfi, C., Edouard, E. & Rassart, E. Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol. 37, 179–191 (2014). https://doi.org/10.1007/s13402-014-0171-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-014-0171-y

Keywords

Search

Navigation