Characterization of Vertebrate Homologs of Drosophila Photoreceptor Proteins

  • Paulo A. Ferreira
  • William L. Pak


In invertebrates, a large body of evidence about the molecular mechanisms governing the visual cascade has been derived from the molecular genetic dissection of the components of the Drosophila photoreceptor machinery (1 – 5). As the best genetically characterized metazoan system, Drosophila provides an advantage in some respects over the mammalian system in that the genes can be both molecularly and genetically dissected facilitating the association of a particular gene product with its in vivo cellular function. Several of the Drosophila mutants identified with changes in the light evoked responses also lead to photoreceptor degeneration. These are of particular interest, as retinal degeneration is a major cause of inherited blindness in humans. In addition, electrophysiological studies in Limulus photoreceptors cells have also provided us with an important insight into the physiology of the invertebrate visual cascade (6).


Outer Segment Photoreceptor Cell Outer Nuclear Layer Photoreceptor Degeneration Vertebrate Retina 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pak, W. L., Grossfield, J., and White, N.V. (1969). Nonphototactic mutants in a study of vision of Drosophila. Nature (London) 222, 351–354.CrossRefGoogle Scholar
  2. 2.
    Pak, W. L., Grossfield, J., and Arnold, K. (1970). Mutants of the visual pathway of Drosophila melanogaster. Nature (London) 227, 518–520.CrossRefGoogle Scholar
  3. 3.
    Pak, W. L. (1979) Study of photoreceptor function using Drosophila mutants. In Breakefield XO (ed): “Neuro genetics: Genetic Approaches to the Nervous System,” New York: Elsevier North Holland, pp 67–99.Google Scholar
  4. 4.
    Pak, W. L. (1991) Molecular genetic studies of photoreceptor function using Drosophila mutants. In D. Farber and G. Chader (ed): “Molecular Biology of the Retina: Basic Clinically Relevant Studies,” New York: Wiley-Liss, Inc. pp 1–32.Google Scholar
  5. 5.
    Ranganathan, R., Harris, W. A., and Zucker, C.S. (1991). The molecular genetics of invertebrate phototransduction. Trends in Neuroscience 14, 486–493.CrossRefGoogle Scholar
  6. 6.
    Payne, R. (1986). Phototransduction by microvillar photoreceptors of invertebrates: mediation of a visual cascade by inositol triphosphate. Photobiochem. Photobiophys. 13, 373–397.Google Scholar
  7. 7.
    Pugh Jr., E. N., and Lamb, T. D. (1990). Cyclic GMP and calcium: the internal messengers of excitation and adaptation in vertebrate photoreceptors. Vision Res. 30, 1923–1948.PubMedCrossRefGoogle Scholar
  8. 8.
    Stryer, L. (1991). Visual excitation and recovery. J. Biol. Chem. 266, 10711–10714.PubMedGoogle Scholar
  9. 9.
    Kaupp, U. B., and Koch, K.-W. (1992). Role of cGMP and Ca2+ in vertebrate photoreceptor excitation and adaptation. Annu. Rev. Physiol. 54, 153–175.PubMedCrossRefGoogle Scholar
  10. 10.
    Wright, A. F. (1992). New insights into genetic eye disease. Trends in Genetics 8, 85–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Hargrave, P. A. and McDowell, J. H. (1992). Rhodopsin and phototransduction: a model system for G-protein-linked receptors. The FASEB J. 6, 2323–2331.Google Scholar
  12. 12.
    O’Tousa, J. E. and Pak, W. L. (1988). Molecular analysis of visual pigments genes. Photobiochem. Photobiol. 47, 877–882.CrossRefGoogle Scholar
  13. 13.
    Palczewski, K., Buczylko, J., Lebioda, L., Crabb, J. and Polans, A. (1993). Identification of the N-terminal region in rhodopsin kinase involved in its interaction with rhodopsin. J. Biol. Chem. 268, 6004–6013.PubMedGoogle Scholar
  14. 14.
    Kelleher, D. J. and Jonhson, G.L. (1986). Phosphorylation of rhodopsin by protein kinase C in vitro. J. Biol. Chem. 261, 4749–4757.PubMedGoogle Scholar
  15. 15.
    Doza, Y.N., Minke, B., Chorev, M. and Selinger, Z. (1992). Characterization of fly rhodopsin kinase. Eur. J. Biochem. 209, 1035–1040.PubMedCrossRefGoogle Scholar
  16. 16.
    Dolf, P. J., Ranaganathan, R., Colley, N. J., Hardy, R. W., Socolich, M. and Zucker, C. S. (1993). Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo. Science 260, 1910–1916.CrossRefGoogle Scholar
  17. 17.
    Gurevich, V. V., and Benovic, J. L. (1993). Visual arrestin interaction with rhodopsin. J. Biol. Chem. 268, 11628–11638.PubMedGoogle Scholar
  18. 18.
    Payne, R., Flores, T. M. and Fein, A. (1990) Feedback inhibition by calcium limits the release of calcium by inositol triphosphate in Limulus ventral photoreceptors. Neuron 4, 547–555.PubMedCrossRefGoogle Scholar
  19. 19.
    Sandier, C. and Kirschfeld, K. (1991). Light-induced extracellular calcium and sodium concentration changes in the retina of Calliphora: involvement in the mechanism of light adaptation. J. Comp. Physiol. 169, 229–311.Google Scholar
  20. 20.
    Hardie, R. C. and Minke, B. (1993). Novel Ca2+ channels underlying transduction in drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization. Trends in Neuroscience 76, 371–376.CrossRefGoogle Scholar
  21. 21.
    Ranganathan, R., Bacskai, B., Tsien, R. and Zucker, C.S. (1994). Cytosolic calcium transients: spatial localization and role in Drosophila photoreceptor cell function. Neuron 13, 837–848.PubMedCrossRefGoogle Scholar
  22. 22.
    Hardie, R. C. (1995). Photolysis of caged Ca2+ facilitates and inactivates but does not directly excite light-sensitive channels in Drosophila photoreceptors. J. Neuroscience 15, 889–902.Google Scholar
  23. 23.
    Fain, G. L. and Matthews, H. R. (1990). Calcium and the mechanism of light adaptation in vertebrate photoreceptors. Trends in Neuroscience 13, 378–384.CrossRefGoogle Scholar
  24. 24.
    Gray-Keller, M. P. and Detwiler, P. B. (1994). The calcium feedback signal in the phototransduction cascade of vertebrate rods. Neuron 13, 849–861.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee, Y.-J., Shah, S., Suzuki, E., Zars, T., O’Day, P. and Hyde, D. R. (1994) The Drosophila dgq gene encodes a Ga protein that mediates phototransduction. Neuron 13, 1143–1157.PubMedCrossRefGoogle Scholar
  26. 26.
    Fung, B. K.-K. (1987) Transducin:structure, function, and role in phototransduction. In Osborne N. N., Chader G. J., eds. “Progress in Retinal Research,” Oxford: Pergamon Press, 6, 151–177.Google Scholar
  27. 27.
    Bloomquist, B. T., Shortridge, R. D., Schneuwly, S., Perdew, M., Montell, C., Steller, H., Rubin, G., and Pak, W. L. (1988). Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Cell 54, 723–733.PubMedCrossRefGoogle Scholar
  28. 28.
    Hotta, Y., and Benzer, S. (1970). Genetic dissection of the Drosophila nervous system by means of mosaics. Proc. Natl. Acad. Sci. USA 67, 1156–1163.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Inoue, H. Yoshioka, T. and Hotta, Y. (1985). A genetic study of inositol triphosphate involvement in phototransduction using Drosophila mutants. Biochem. Biophys. Res. Commun. 132, 513–519.PubMedCrossRefGoogle Scholar
  30. 30.
    Meyertholen, E. P., Stein, P. J., Williams, M. A., and Ostroy, S. E. (1987). Studies of the Drosophila norpA phototransduction mutant, II. Photoreceptor degeneration and rhodopsin maintenance. J. Comp. Physiol. 161, 793–798.CrossRefGoogle Scholar
  31. 31.
    Bowes, C., Li, T. Danciger, M., Baxter, L., Applebury, M., and Farber, D. (1990) Retinal degeneration in the rd mouse is caused by a defect in the b subunit of the rod cGMP-phosphodiesterase. Nature 347, 677–680.PubMedCrossRefGoogle Scholar
  32. 32.
    Lem, J., Flannery, J., Li, T., Applebury, M., Färber, D. and Simon, M. (1992) Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase b subunit. Proc. Natl. Acad. Sci. USA 89, 4422–4426.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Farber, D. B. and Lolley, R. N. (1974) Cyclic guanosine monophosphate: elevations in degenerating photoreceptor cells of the C3H mouse retina. Science 186, 449–451.PubMedCrossRefGoogle Scholar
  34. 34.
    Farber, D. B. and Lolley, R. N. (1976) Enzymatic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina. J. Cyclic Nucleotide Res. 2, 139–148.PubMedGoogle Scholar
  35. 35.
    Hardie, R. and Minke, B. (1992). The trp gene is essential for a light-activated Ca2+ channle in Drosophila photoreceptors. Neuron 8, 643–651.PubMedCrossRefGoogle Scholar
  36. 36.
    Phillips, A. M., Bull, A. and Kelly, L. E. (1992) Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene. Neuron 8, 631–642.PubMedCrossRefGoogle Scholar
  37. 37.
    Yau, K.-W. (1994). Phototransduction mechanism in retinal rods and cones. Invest. Ophtalmol. Vis. Sci. 36, 263–275.Google Scholar
  38. 38.
    Johnson, E. C., Robinson, P. R., and Lisman, J. E. (1986). Cyclic GMP is involved in the excitation of invertebrate photoreceptors. Nature 324, 468–470.PubMedCrossRefGoogle Scholar
  39. 39.
    Bacigalupo, J., Johnson, E., Vergara, C., and Lisman, J. (1991). Light-dependent channels from excised patches of Limulus ventral photoreceptors are open by cGMP. Proc. Natl. Acad. Sci. USA 88, 7938–7942.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Fein, A., Payne, R., Corson, D. W., Berridge, M. J. and Irvine, R. (1984) Photoreceptor excitation and adaptation by inositol 1,4,5-triphosphate. Nature 311, 157–160.PubMedCrossRefGoogle Scholar
  41. 41.
    Brown, J., Rubin, L., Ghalayini, A., Tarver, A., Irvine, R., Berridge, M. and Anderson, R. E. (1984) Myo-inositol polyphosphate may be a messenger for visual excitation in Limulus phootreceptors. Nature 311, 160–162.PubMedCrossRefGoogle Scholar
  42. 42.
    Shin, J., Richard, E. and Lisman, J. E. (1993). Ca2+ is an obligatory intermediate in the excitation cascade of Limulus photoreceptors. Neuron, 77, 845–855.CrossRefGoogle Scholar
  43. 43.
    Anderson, R. E., and Brown, J. E. (1988). Phosphoinositides in the retina. In Osborne N. N. and Chader G. J., eds. “Progress in Retinal Research,” Oxford: Pergamon Press, 9, 211–228.Google Scholar
  44. 44.
    Das, N. D., Yoshioka, T., Samuelson, D., and Shichi, H. (1986). Immunocytochemical localization of phosphatidyl-4,5-biphosphate in dark-and light-adapted rat retinas. Cell Struc. Funct. 77, 53–63.CrossRefGoogle Scholar
  45. 45.
    Gehm, B. D., and McConnel, D. G. (1990). Phosphatidylinositol-4,5-biphosphate phospholipase C in bovine rod outer segments. Biochemistry 29, 5447–5452.PubMedCrossRefGoogle Scholar
  46. 46.
    Ghalayini, A., and Anderson, R. E. (1984). Phosphatidylinositol 4,5-bisphosphate: light-mediated breakdown in the vertebrate retina. Biochem. Biophys. Res. Comm. 124, 503–506.PubMedCrossRefGoogle Scholar
  47. 47.
    Hayashi, F., and Amakawa, T. (1985). Light-mediated breakdown of phosphatidylinositol-4,5-biphosphate in isolated rod outer segments of frog photoreceptor. Biochem. Biophy. Res. Comm. 128, 954–959.CrossRefGoogle Scholar
  48. 48.
    Jelsema, C. L. (1989). Regulation of phospholipase A2 and phospholipase C in rod outer segments of bovine retina involves a common GTP-binding protein but different mechanisms of action. Ann. N. Y. Acad. Sci. 559, 158–177.PubMedCrossRefGoogle Scholar
  49. 49.
    Jelsema, C. L., and Axelrod, J. (1987). In Sensory Transduction (Discussions in Neurosciences), Hudspeth, A., Macleish, P., Margolis, F. eds. (Foundations for the Study of the Nervous System, Geneva), Vol. 4, 79–84.Google Scholar
  50. 50.
    Millar, F., and Hawthorne, J. (1985). Polyphosphoinositide metabolism in response to light stimulation of retinal rod outer segments. Biochem. Soc. Trans. 13, 984–985.Google Scholar
  51. 51.
    Millar, F. A., Fisher, S. C., Muir, C. A., Edwards, E., and N., H. J. (1988). Polyphosphoinositide hydrolysis in response to light stimulation of rat and chick retina and retinal rod outer segments. Biochem. Biophys. Acta 970,205–211.PubMedCrossRefGoogle Scholar
  52. 52.
    Yoshioka, T., and Inoue, H. (1987). Inositol phospholipid in visual excitation. Neurosc. Res. Suppl. 6, S15–S24.CrossRefGoogle Scholar
  53. 53.
    Ghalayini, A., Tarver, A., Mackin, W.M., Koutz, C.A. and Anderson, R. E. (1991) Identification and immunolocalization of phospholipase C in bovine rod outer segments. J. Neurochem. 57, 1405–1412.PubMedCrossRefGoogle Scholar
  54. 54.
    Peng, Y.-W., Sharp, A. H., Snyder, S. H., and Yau, K.-W. (1991). Localization of the inositol 1,4,5-triphosphate receptor in synaptic terminals in the vertebrate retina. Neuron 6, 525–531.PubMedCrossRefGoogle Scholar
  55. 55.
    Day, N. S., Koutz, C. A. and Anderson, R. E. (1993). Inositol-1,4,5-trisphosphate receptors in the vertebrate retina. Current Eye Res. 12, 981–992.CrossRefGoogle Scholar
  56. 56.
    Bonigk, W., Altenhofen, W., Muller, F., Dose, A., Illing, M., Molday, R. S., and Kaupp, U. B. (1993). Rod and cone photoreceptor cells express distinct genes for cGMP-gated channels. Neuron 10, 865–877.PubMedCrossRefGoogle Scholar
  57. 57.
    Haynes, L. W., and Yau, K.-W. (1990). Single channel measurement from the cGMP-activated conductance of catfish retinal cones. J. Physiol. 429, 451–481.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Lerea, C. L., Bunt-Milam, A. H., and Hurley, J. B. (1989). a-transducin is present in blue-, green-,and red-sensitive cone photoreceptors in the human retina. Neuron 3, 367–376.PubMedCrossRefGoogle Scholar
  59. 59.
    Li, T., Volpp, K., and Applebury, M. L. (1990). Bovine cone photoreceptor cGMP phosphodiesterase structure deduced from a cDNA clone. Proc. Natl. Acad. Sci. USA 87, 293–297.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Tomita, T. (1965). Electrophysiological study of the mechanisms subserving color coding in the fish retina. Cold Spring Harb. Symp. Quant. Biol. 30, 559–566.PubMedCrossRefGoogle Scholar
  61. 61.
    Solessio, E., and Engbretson, G. A. (1993). Antagonistic chromatic mechanisms in photoreceptors of the parietal eye of lizards. Nature 364, 442–445.PubMedCrossRefGoogle Scholar
  62. 62.
    Rohlich, P., van Veen, Th. and Szel, A. (1994). Two different visual pigments in one retinal cone cell. Neuron 13, 1159–1166.PubMedCrossRefGoogle Scholar
  63. 63.
    Rhee, S.-G., Suh, P.-G., Ryu, S.-H., and Lee, S. (1989). Studies of inositol phospholipid-specific phospholipase C. Science 244, 546–550.PubMedCrossRefGoogle Scholar
  64. 64.
    Ferreira, P., Shortridge, R. and Pak, W. (1991). Identification and characterization of norpA-like retina-specific bovine cDNA”. Molecular Neurobiology of Drosophila, pg. 51, Cold Spring Harbor, New York.Google Scholar
  65. 65.
    Ferreira, P. and Pak, W. (1992). Retina-specific bovine cDNAs encoding homologs of the norpA and ninaA proteins of Drosophila. Society for Neuroscience, vol. 18, pg.137.Google Scholar
  66. 66.
    Ferreira, P., Shortridge, R., and Pak, W. (1993). Distinctive subtypes of bovine phospholipase C that have preferential expression in the retina and high homology to the norpA gene product of Drosophila. Proc. Natl. Acad. Sci. USA 90, 6042–6046.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Nakagawa, T., Okano, H., Furuichi, T., Aruga, J., and Mikoshiba, K. (1991). The subtypes of the mouse inositol 1,4,5-triphosphate receptor are expressed in a tissue-specific and developmentally specific manner. Proc. Natl. Acad. Sci. USA 88, 6244–6248.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Shortridge, R., Yoon, J., Lending, C., Bloomquist, B., Perdew, M., and Pak, W. (1991). A Drosophila phospholipase C gene that is expressed in the central nervous system. J. Biol. Chem. 266, 12474–12480.PubMedGoogle Scholar
  69. 69.
    Katan, M., Kriz, R., Totty, N., Philip, R., Moldrum, E., Aldape, R., Knopf, J., and Parker, P. (1988). Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities. Cell 54, 171–177.PubMedCrossRefGoogle Scholar
  70. 70.
    Park, D., Jhon, D.-Y, Kriz, R., Knopf, J. and Rhee, S. G. (1992). Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-b2. J. Biol. Chem. 267, 16048–16055.PubMedGoogle Scholar
  71. 71.
    Stahl M.L., Ferenz, C.R., Kelleher, K.L., Kriz, R.W., Knopf, J.L. (1988). Sequence similarity of phospholipase C with the non-catalytic region of src. Nature 332, 269–272.PubMedCrossRefGoogle Scholar
  72. 72.
    Shu, P.-G., Ryu, S., Moon, K.H., Suh, H.W. and Rhee, S. G. (1988). Cloning and sequencing of multiple forms of phospholipase C. Cell 54, 161–169.CrossRefGoogle Scholar
  73. 73.
    Bourne, H. R., Sanders, D. A., and McCormick, F. (1991). The GTPase superfamily: conserved structure and molecular mechanism. Nature (London) 349, 117–127.CrossRefGoogle Scholar
  74. 74.
    Rechsteiner, M. (1990). PEST sequences are signals for rapid intracellular proteolysis. Sem. Cell Biol. 1, 433–440.Google Scholar
  75. 75.
    Carter-Dawson, L. and LaVail, M. (1979). Rods and cones in the mouse retina. J. Comp. Neur. 188, 245–262.PubMedCrossRefGoogle Scholar
  76. 76.
    Ferreira, P. and Pak, W. (1994). Bovine phospholipase C highly homologous to the norpA protein of Drosophila expressed specifically in cones. J. Biol. Chem., 269, 3129–3131.PubMedGoogle Scholar
  77. 77.
    Schneuwly, S., Burg, M., Lending, C., Perdew, M., and Pak, W. L. (1991). Proprieties of photoreceptor-specific phospholipase C encoded by the norpA gene of Drosophila melanogaster. J. Biol. Chem. 266, 24314–24319.PubMedGoogle Scholar
  78. 78.
    Zhu, L., McKay, R., and Shortridge, R. (1993). Tissue-specific expression of phopholipase C encoded by the norpA gene of Drosophila melanogaster. J. Biol. Chem. 268, 15994–16001.PubMedGoogle Scholar
  79. 79.
    Min, D. S., Kim, D., Lee, Y., Seo, J., Suh, P.-G. and Ryu, S. H. (1993) Purification of a novel phospholipase C isozyme from bovine cerebellum. J. Biol. Chem. 268, 12207–12212.PubMedGoogle Scholar
  80. 80.
    Lee, C.-W., Park, D. J., Lee, K.-H., Kim, C. G., and Rhee, S. G. (1993). Purification, molecular cloning, and sequencing of phospholipase C-b4. J. Biol. Chem., 268, 21318–21327.PubMedGoogle Scholar
  81. 81.
    Stephenson, R. S., O’Tousa, J., Scavarda, N. J., Randall, L. L., and Pak, W. L. (1983). Drosophila mutants with reduced opsin content. In D. J. Cosens, & D. Vince-Price (Ed.), The Biology of Photoreception (pp. 447–501). Soc. Exp. Biol., Cambridge, U.K.: Cambridge University Press.Google Scholar
  82. 82.
    Larrivee, D. C., Conrad, S. K., Stephenson, R. S., and Pak, W. L. (1981). Mutation that selectively affect rhodopsin concentration in the peripheral photoreceptors of Drosophila. J. Gen. Physiol. 78, 521–545.PubMedCrossRefGoogle Scholar
  83. 83.
    Schneuwly, S., Shortridge, R., Larrivee, D., Ono, T., Ozaki, M., and Pak, W. (1989). Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). Proc. Natl. Acad. Sci. USA 86, 5390–5394.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Shieh, B.-H., Stamnes, M. A., Seavello, S., Harris, G. L., and Zuker, C. S. (1989). The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein. Nature 338, 67–70.PubMedCrossRefGoogle Scholar
  85. 85.
    Stamnes, A. M., Shieh, B.-H., Chuman, L., Harris, L. G., and Zuker, C. S. (1991). The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins. Cell 65, 219–227.PubMedCrossRefGoogle Scholar
  86. 86.
    Fisher, G., Wittmann-Liebold, B., Lang, K., Kiefhaber, T., and Schmid, F. X. (1989). Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337, 476–478.CrossRefGoogle Scholar
  87. 87.
    Takahashi, N., Hayano, T., and Suzuki, M. (1989). Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337, 473–475.PubMedCrossRefGoogle Scholar
  88. 88.
    Ondek, B., Hardy, R., Baker, E., Stamnes, M., Shieh, B.-H., and Zuker, C. (1992). Genetic dissection of cyclophilin function. J. Biol. Chem. 267, 16460–16466.PubMedGoogle Scholar
  89. 89.
    Baker, E.K., N.C. Colley, & Zuker, C.S. (1994). The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J. 13, 4886–4895.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Ferreira, P. and Pak, W. (1993). Retina-specific bovine homologs of ninaA. Molecular Neurobiology of Drosophila, pg. 158, Cold Spring Harbor, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Paulo A. Ferreira
    • 1
  • William L. Pak
    • 2
  1. 1.Psychiatry and Neuroscience DepartmentUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Biological SciencesPurdue UniversityWest LafayetteUSA

Personalised recommendations