Research in my lab in collaboration with Dr. Imara Perera focused on the role of inositol phospholipids in regulating plant sensing and response to environmental stimuli including osmotic stress and gravity. We took a combinatorial approach that includes biochemistry, cell biology and molecular biology to characterize the enzymes involved in inositol lipid biosynthesis, to study their subcellular distribution and to genetically alter the flux through the PI signaling pathway. In addition, in collaboration with Dr. Amy Grunden, we took a molecular genetics approach to reduce the presence or reactive oxygen species in plants by expressing genes from Pyrococcus furiosus.
Ma, X., O. Shor, S. Diminstein, L. Yu, Y.J. Im, I.Y. Perera, A. Lomax, , W.F. Boss, M. Nava Moran, 2009. Phosphatidylinositol (4,5)-bisphosphate inhibits K+-efflux channel activity in NT1 tobacco cultured cells. Plant Physiology 149:1127-1140.
Perera, I.Y., C.-Y. Hung, C.D. Moore, J. Stevenson-Paulik, W. F. Boss, 2008. Transgenic Arabidopsis plants expressing the type 1 inositol 5-phosphatase exhibit increased drought tolerance and altered ABA signaling. The Plant Cell 20:2876-2893.
Galvão, R.M., U. Kota, E. J. Soderblom, M. B. Goshe, W. F. Boss, 2008. Characterization of a new family of protein kinases containing phosphoinositide 3/4-kinase and ubiquitin-like domains. Biochemistry Journal. 409:117-127.
Im, Y.J., I.Y. Perera,, I. Brglez, A.J. Davis, J. Stevenson-Paulik, B.Q. Phillippy, E. Johannes, N.S. Allen, W. F. Boss, 2007. Increasing plasma membrane phosphatidylinositol(4,5)bisphosphate biosynthesis increases phosphoinositide metabolism. The Plant Cell, 19: 1603-1616.
Im, Y.J., A.J. Davis, I.Y. Perera, E. Johannes, N.S. Allen, W. F. Boss. 2007. The N-terminal membrane occupation and recognition nexus domain of Arabidopsis phosphatidylinositol phosphate kinase 1 regulates enzyme activity. J. Biological Chemistry. 282: 5443-5452
Perera, I.Y., C.Y. Hung, S. Brady, G. K. Muday,W. F. Boss. 2006.A Universal Role for Inositol 1,4,5-Trisphosphate-Mediated Signaling in Plant Gravitropism Plant Physiol., 140: 746-760.
Im, Y.J., M. Ji, A.M. Lee, W. F. Boss, A.M. Grunden, 2005. Production of a thermostable archaeal superoxide reductase in plant cells. FEBS Letters. 579:5521-5526.
Perera, I.Y., A.J. Davis, D.Galanopoulou, Y.J. Im, W.F. Boss. 2005.Characterization and comparative analysis of Arabidopsis phosphatidylinositol phosphate 5-kinase 10 reveals differences in Arabidopsis and human phosphatidylinositol phosphate kinases. FEBS Letters. 579:3427-3432.
Akesson, A., Staffan, P. Love, J., Boss, W.F., Widell, S. Sommarin,M. 2005.Overexpression of the Ca2+-binding protein calreticulin in the endoplasmic reticulum improves growth of tobacco cell suspensions (Nicotiana tabacum) in high-Ca2+ medium Physiologia Plantarum 123:92-99.
Kimbrough, J., R. Salinas-Mondragon, W.F. Boss, C.S. Brown, H. Winter Sederoff. 2004. The fast and transient transcriptional network of gravity and mechanical stimulation in the Arabidopsis root apex. Plant Physiol. 136: 2790-2805.
Davis, A.J., I.Y. Perera, W. F. Boss 2004. Cyclodextrins enhance recombinant phosphatidylinositol phosphate kinase activity J. Lipid Res. 45: 1783-1789.
Persson S.H., M. Rosenquist, K. Svensson, R. Galvão, W. F. Boss, M. Sommarin 2003. Phylogenetic Analyses and Expression Studies Reveal Two Distinct Groups of Calreticulin Isoforms in Higher Plants Plant Physiol. 133: 1385-1396
Stevenson-Paulik, J.M., J. Love, W. F. Boss 2003. Differential Regulation of two Arabidopsis Type III Phosphatidylinositol 4-Kinase Isoforms: A regulatory role for the pleckstrin homology domain. Plant Physiol. 132: 1053-1064.
Perera, I.Y., J. Love, I. Heilmann, W.F. Thompson, W.F. Boss. 2002 Up-regulation of Phosphoinositide Metabolism in Tobacco Cells Constitutively Expressing the Human Type I Inositol Polyphosphate 5-Phosphatase. Plant Physiology 129:1795-1806.
Persson S.H. J. Love, P-L Tsou, D. Robertson, W.F. Thompson, W.F. Boss 2002 When a day makes a difference. Interpreting data from endoplasmic reticulum-targeted green fluorescent protein fusions in cells grown in suspension culture. Plant Physiology 128:341-344
Heilmann I., I.Y. Perera, W.Gross, W.F. Boss 2001 Plasma membrane phosphatidylinositol 4,5-bisphosphate levels decrease with time in culture. Plant Physiol 126: 1507-1518
Persson S.H., S.E. Wyatt, J. Love, W.F. Thompson, D. Robertson, and W.F. Boss 2001 The Ca2+ status of the Endoplasmic Reticulum is Altered by Transgenic Calreticulin Expression in Plants. Plant Physiol. 126: 1092-1104
Shank, K.J., P. Su, I. Brglez, W.F. Boss, R.E. Dewey, and R. S. Boston 2001 Induction of lipid metabolic enzymes during the ER stress response in plants. Plant Physiol. 126: 267-277.
Perera, I.Y., Heilmann, I, Chang, S.C., Boss, W.F. and Kaufman P.B. 2001 A role for inositol 1,4,5 trisphosphate in gravitropic signaling and the retention of cold-perceived gravistimulation of oat (Avena sativa) shoot pulvini. Plant Physiology 125:1499-1507.
Ransom-Hodgkins, W.D., I. Brglez, X. Wang and W.F. Boss. 2000 Calcium-regulated proteolysis of eEF1A. Plant Physiology 122:957-966
Perera, I.Y., Heilmann, I. and W.F. Boss. 1999. Transient and sustained increases in inositol 1,4,5-trisphosphate precede the differential growth response in gravistimulated maize pulvini. Proc Natl Acad Sci 96:5838-5843.
Heilmann, I., I.Y. Perera, W. Gross and W.F. Boss. 1999. Changes in phosphoinositide metabolism with days in culture affect signal transduction pathways in Galdieria sulphuraria. Plant Physiology 119:1331-1340.
Stevenson, J.M., I.Y. Perera and W.F. Boss. 1998. A Phosphatidylinositol 4-kinase Pleckstrin Homology (PH) Domain that Binds Phosphatidylinositol 4-Monophosphate. J. Biol Chem. 273:22761-22767.
Ransom, W.D., P.-C. Lao, D. Gage, and W.F. Boss. 1998. Phosphoglycerylethanolamine Posttranslational Modification of Plant eEF-1A. Plant Physiology. 117:949-960.
Tucker E.B. and W. F. Boss. 1996. Mastoparan-induced intracellular Ca2+ fluxes may regulate cell-to-cell communication in plants. Plant Physiology 111:459-467.
Cho, M. H., Z. Tan, C. Erneux, S. B. Shears, and W. F. Boss. 1995. The effects of mastoparan on the carrot cells plasma membrane polyphosphoinositide phospholipase C. Plant Physiology 107:845-856.
Okpodu, C. M., W. Gross, W. Burkhart, and W. F. Boss. 1995. Purification and characterization of a soluble phosphatidylinositol 4-kinase from carrot suspension culture cells. Plant Physiology 107:491-500.
Yang, W. and W.F. Boss. 1994. Regulation of the Plasma Membrane Type III Phosphatidylinositol 4-Kinase by Positively Charged Compounds. Archives of Biochem Biophys. 313:112-119.
Okpodu, C. M., D. Robertson, W. F. Boss, R. K. Togasaki, and S. J. Surzycki. 1994 Rapid isolation of nuclei from carrot suspension culture cells using a Bionebulizer. Biotechniques 16:154-157.
Borochov, A., M. H. Cho, W. F. Boss. 1994 Plasma membrane lipid metabolism of petunia petals during senescence. Physiol. Plant. 90:279-284.
Yang, W. and W.F. Boss. 1994. Regulation of the Phosphatidylinositol 4-kinase Activity by the Protein Activator PIK-A49. Activation Requires Protein Phosphorylation. J Biol Chem. 269:3852-3857.
Cho, M. H., S. B. Shears and W. F. Boss. 1993. Changes in Phosphatidylinositol Metabolism in Response to Hyperosmotic Stress in Daucus carota L. Cells Grown in Suspension Culture. Plant Physiol. 103:637-647.
Yang, W., W. Burkhart, J. Cavallius, W.C. Merrick, and W. F. Boss. 1993. Purification and Characterization of a Phosphatidylinositol 4-Kinase Activator in Carrot Cells. J Biol Chem. 268: 392-289.
Tan, Z. and W. F. Boss. 1992. Association of Phosphatidylinositol Kinase, Phosphatidylinositol Monophosphate Kinase and Diacylglycerol Kinase with the Cytoskeleton and F-actin Fractions of Carrot (Daucus carota L.) Cells Grown in Suspension Culture: Response to Cell Wall Degrading Enzymes. Plant Physiology 100: 2116-2120.
Gross, W., W. Yang and W. F. Boss. 1992. Release of Plasma Membrane- associated Phosphatidylinositol Kinase by Phospholipase A2 and Activation by a 70-kDa Protein. Biochim Biophys Acta. 1134: 73-80.
Cho, M.H., Q. Chen, C.M. Okpodu, and W. F. Boss. 1992. Separation and quantitation of [3H]inositol phospholipids using thin-layer chromatography and a computerize 3H imaging scanner. LC-GC 10: 464-468.
Wheeler, J.J., W. Gross, H. Assefa and W.F. Boss. 1991. Phosphorylation of Lysophosphatidylinositol by Plasma Membranes Isolated from Carrot Cells. Biochim Biophys Acta. 1086: 310-316.
Chen, Q. and W. F. Boss. 1991. Neomycin Inhibits the PIP and PIP2 Stimulation of Plasma Membrane ATPase Activity. Plant Physiol. 96: 340-343.
Chen, Q. and W. F. Boss. 1990. Activation of Phosphatidylinositol Monophosphate Kinase and ATPase Activity by Cell Wall Digestion Enzymes. Plant Physiol. 94: 1820-1829.
Memon, A. and W. F. Boss. 1990. Rapid Light-induced Changes in Phosphoinositide Kinases and ATPase Activity in Sunflower Hypocotyls. J. Biol. Chem. 265: 14817-14821.
Van Breemen, R., J. J. Wheeler, W. F. Boss. 1990. Negative Ion Fast Atom Bombardment Mass Spectrometry of Plant Phosphoinositides. Lipids. 25:328-334.
Memon, A., Q. Chen, and W. F. Boss. 1989. Inositol Phospholipids Activate Plasma Membrane ATPase in Plants. Biochem Biophys Research Comm. 162:1295-1301.
Memon, A., M. Rincón and W. F. Boss. 1989. Inositol Trisphosphate Metabolism in Carrot (Daucus carota L.) Cells. Plant Physiol. 91:477-480.
Wheeler, J. J. and W. F. Boss. 1989. The Presence of sn-1-Palmitoyl Lysophosphatidylinositol Monphosphate Correlates Positively with the Fusogenic State of the Plasma Membrane of Fusogenic Carrot Cells Grown in Suspension Culture. Biochim Biophys Acta. 984:33-40.
Hendrix, K. W., H. A. Assefa and W. F. Boss. 1989. Polyphosphoinositides are Present in Nuclei Isolated from Carrot Protoplasts. Protoplasma. 151:62-72.
Rincón, M. Q. Chen, and W. F. Boss. 1989. Characterization of Inositol Phosphates in Carrot (Daucus carota L.) Cells. Plant Physiology. 89:126-132.
Blowers, D., W. F. Boss, and A. J. Trewavas. 1988. Rapid Changes in Plasma Membrane Protein Phosphorylation During Cell Wall Digestion. Plant Physiol. 86:505-509.
Wheeler, J. J. and W. F. Boss. 1987. Polyphosphoinositides are Present in the Plasma Membranes Isolated from Fusogenic Carrot Cells. Plant Physiol. 85:389-392.
Rincón, M. and W. F. Boss. 1987. Myo-Inositol Trisphosphate Mobilizes Calcium from Fusogenic Carrot (Daucus carota L.) Protoplasts. Plant Physiol. 83:395-398.
Kanchanapoom, K. and W. F. Boss. 1986. Osmoregulation of Fusogenic Protoplast Fusion. Biochim Biophys Acta. 861:419-439.
Kanchanapoom, K. and W. F. Boss. 1986. The Effect of Fluorescent Labeling on Calcium-induced Fusion of Fusogenic Carrot Protoplasts. Plant Cell Reports 5:252-255.
Grimes, H. D., W. Slocum, and W. F. Boss. 1986. Difluoro-methylarginine Inhibits Protoplast Fusion in Fusogenic Carrot Protoplasts. Biochim Biophys Acta. 886:130-134.
Boss, W. F. and M. O. Massel. 1985. Polyphosphoinositides are Present in Plant Tissue Culture Cells. Biochem Biophys Res Comm. 132:1018-1023.
Grimes, H. D. and W. F. Boss. 1985. Intracellular Calcium and Calmodulin Involvement in Protoplast Fusion. Plant Physiol. 79: 253-258.
Kanchanapoom, K., H. D. Grimes, A. O. Brightman, and W. F. Boss. 1985. A Novel Method for Monitoring Protoplast Fusion. Protoplasma. 124:65-70.
Boss, W. F., H. D. Grimes, and A. O. Brightman. 1984. Calcium-induced Fusion of Fusogenic Wild Carrot Protoplasts. Protoplasma. 120:209-215.
Boss, W. F., D. J. Morré, H. H. Mollenhauer. 1984. Monensin-induced Swelling of Golgi Apparatus Cisternae Mediated by a Proton Gradient. European J Cell Biol. 34:1-8.
Morré, D. J., W. F. Boss, and H. H. Mollenhauer. 1984. Distribution of Golgi Apparatus-associated Polyribosomes Across the Polarity Axis of Dictyosomes of Wild Carrot (Daucus carota L.). Protoplasma. 123:213-220.
Gripshover, B., D. J. Morré, and W. F. Boss. 1984. Fractionation of Suspension Cultures of Wild Carrot and Kinetics of Membrane Labeling. Protoplasma. 123:221-225.
Boss, W. F. 1983. PEG-induced Fusion of Plant Protoplasts: A Spin Label Study. Biochim Biophys Acta. 730:111-118.
Morré, D. James, W. F. Boss, Howard Grimes, and Hilton H. Mollenhauer. 1983. Kinetics of Golgi Apparatus Membrane Flux Following Monensin Treatment of Embryogenic Carrot Cells. European J of Cell Biol. 30:25-32.
Grimes, H. D., K. K. Perkins, W. F. Boss. 1983. Ozone Degrades into Hydroxyl Radicals Under Physiological Conditions: A Spin Trapping Study. Plant Physiol. 72:1016-1020.
Boss, W. F. and R. L. Mott. 1980. The Effects of Divalent Cations and Polyethylene Glycol on Membrane Fluidity of Protoplasts. Plant Physiol. 66:835-837.
Boss, W. F. and Albert W. Ruesink. 1979. Isolation and Characterization of Concanavalin A-labeled Plasma Membranes from Carrot Suspension Culture Cells. Plant Physiol. 65:1005-1011.
Boss, W. F., C. J. Kelley, and F. R. Landsberger. 1975. A Novel Synthesis of Spin Label Derivatives of Phosphatidylcholine. Analytical Biochem. 65:289-292.
Craig, A. R., K. C. Das, W. J. Farmer, Yu-Yin Lin, Wai-Kaun Woo, and B. Weinstein. 1971. Constituents of the Leaves and Root Bark of Ceanothus velutinus. Phytochem. 10:908-909.
Das, K. C., W. J. Farmer, and B. Weinstein. 1970. Phytochemical Studies. IX. A New Flavone Velutin. J Org Chem. 35:3989-3990.
COMMENTARIES AND PUBLIC PRESS/RADIO:
ASPB Newsletter: – May/June 2005 – Women in Plant Biology column- “Tapping the Puzzle Piece: The Legacy of Pride in Science” by Jessica T. Farmer and W.F. Boss
Henry Bortman, “Martian Gardens”, Astrobiology Magazine, February, 26, 2006. Website:
Jamais Cascio, “Plant Stress and Changing Environments”, in Wold Changing website: Website: www.worldchanging.com/archives/003289.html
Micheal Kulikowski, “NC State Researchers Redesign Life for Mars and Beyond”, NCSU News Services press release Website: http://www.ncsu.edu/news/press_releases/05_10/204.htm
Eleanor Mayne, “Plant Life on Mars? NASA Scientists Create Alien Crops to Thrive in the Red Plant’s Lethal Atmosphere” The Mail on Sunday, October 16, 2005.
Karen Miller, “Prozac for Plants”, Marsbugs: the Electronic Astrobiology Newsletter, Vol. 12:28, August 19, 2005 Website: http://www.lyon.edu/projects/marsbugs/2005/20050819.pdf
The “Prozac for Plants” article was also featured in “The Spectrum: A Roper Mountain Astonomer’s Publication” Website: http://www.rmastro.com/spectrum/rma-spectrum-08-2005.pdf
Interviewed by Robert Mcdonald of the Canadian Broad Casting Company, for his radio show “Quirks & Quarks” which aired November 26, 2005. Website: http://radio.cbc.ca/programs/quirks/archives/05-06/nov26.html
North Carolina Research Perspective, the News magazine for North Carolina Agricultural Research Services in the College of Agriculture and Life Sciences, “College researchers mine microbes for genes that may help plants in extreme environments.” Website: http://www.cals.ncsu.edu/agcomm/magazine/winter06/microbes.html
Tracy Staedter, “Building Tough Crops to Grow on Mars” The Discovery Channel Online. September 1, 2006
Featured on the websites ScienceDaily, “How Do You Get Plants To Grow On Mars? The First Step: Relieve Their Anxiety.” http://www.sciencedaily.com/releases/2005/08/050807105422.htm
The “How Do You Get Plants To Grow On Mars? The First Step: Relieve Their Anxiety” story was also archived on the Public Understanding of Biotechnology, Biotechnology in the News. Website:www.pub.ac.za/news/bioinnews/2005_aug.html
Interviewed by Chantal Srivastava of Québec Science. Published July 2007
Interviewed by William Weir of the Hartford, Ct Courant for his March 22, 2007 article entitled “No “Advanced Concepts” In NASA’s Future?”
Interviewed by BBC Radio 4 for the program Tulips On The Moon, presented by Richard Hollingham and produced by Fiona Roberts.
BOOK CHAPTERS OR REVIEWS:
Boss, W.F., Lynch, D.V. Wang, X. 2008. Lipid-Mediated Signaling. In: Intracellular Signaling in Plants. ed., Z. Yang, Chapter 8 pp 232-243.
Boss, W.F. A.J. Davis, Y.J. Im, R.M. Galvao and I.Y. Perera. 2006 Phosphoinositide Metabolism: Towards an Understanding of Subcellular Signaling In: Biology of Inositols and Phosphoinositides, Subcellular Biochemistry, ed. Lahiri Majumder vol 39:181-205
Heilmann I., I.Y. Perera, W.F. Boss (2002) An Evolutionary Perspective of Phosphoinositide Signaling During Osmotic Stress. V. Kravets et al., eds. In Intracellular Signalling in Plant and Animal Systems.
Perera, I.Y., I. Heilmann, W.F. Boss. The Phosphoinositide (PI) Pathway and Signaling in Plants. In: Signal Transduction in Plants: Current Advances. Eds. S.K. Sopory, R. Oelmuller and S.C. Maheshwari, Kluwer Academic/Plenum Inc
Heilmann I., Perera I.Y., Stevenson J.M., and Boss 2000. Sense and Sensibility: Phosphoinositide signaling and osmotic stress. In Plant Tolerance to Abiotic Stresses in Agriculture: Role of Genetic Engineering, JH Cherry, Robert Locy and AM Rychter eds. NATO Advanced Workshop, pp 285-296
Stevenson, J.M., I.Y. Perera, I Heilmann, S Persson, W.F. Boss. 2000. Inositol Signaling and Plant Growth, Trends in Plant Science 5:252-257
Drøbak, B.K., R.E. Dewey, and W. F. Boss. 1999. Phosphoinositide-Kinases and the Synthesis of Polyphosphoinositides in Higher Plant Cells. International Review of Cytology-A survey of Cell Biology, K.W. Jeon ed., CRC Press, 189:95-130.
Heilmann I., Perera I.Y., Stevenson J.M., Ransom W.D., Gross W. and Boss W.F. (1998) Inositol lipid signaling: What can we learn from plants? In: Advances in Lipids Research. eds., J Sanchez, E Cerda-Olmedo and E Martinez-Force. University of Sevilla Press, Sevilla, Spain pp394-397.
Perera, I.Y. and W.F. Boss. 1996. Signal Transduction Pathways : A plant perspective of inositol metabolism and growth. In: Regulation of Plant Growth and Development by Light. W. R. Briggs, R. L. Heath, E. M. Tobin eds., Am Soc. Plant Physiol.. USA, pp 114-126.
Boss, W.F, W. Yang, Z. Tan, and M. Cho. 1995. Regulation of phosphatidylinositol 4-kinase by protein phosphorylation: A plasma membrane cytoskeletal connection. In: Plant Lipid Metabolism, J-C. Kader and P. Mazliak eds., Kluwer Academic Publishers, The Netherlands. pp 219-223.
Cho, M.H. and W. F. Boss. 1995. Transmembrane Signalling and Phosphoinositides. In: Methods in Cell Biology. D. Galbraith, D. Bourque, Hans Bohnert eds. Academic Press, New York. vol. 49, pp 543-554.
Gross, W. and W. F. Boss. 1993. Inositol Phospholipids and Signal Transduction. In: Control of Plant Gene Expression D.P.S. Verma, ed. The Telford Press, Caldwell, New Jersey. pp 17-32.
Chen, Q, I Brglez and W. F. Boss. 1991. Inositol Phospholipids as Plant Second Messengers. In: Jenkins G and W Schuch, eds. Molecular Biology of Plant Development. Company of Biologists, Cambridge. pp 159-175.
Boss, W. F., A. R. Memon, and Q. Chen. 1990. Phospholipid-Derived Second Messengers. In: Signal Perception and Transduction in Higher Plants. R. Ranjeva and A. M. Boudet, eds. NATO ASI Series Vol 47. Springer-Verlag, Berlin. pp 160-184.
Rincón, M. and W. F. Boss. 1990. Phosphoinositides as Second Messengers in Plants. In: Plant Inositide Metabolism. D. J. Morré, W. F. Boss and F. Loewus, eds. Wiley-Liss, New York. pp 173-200.
Wheeler, J. J. and W. F. Boss. 1990. Inositol Lysolipids. In: Plant Inositides. D. J. Morré, W. F. Boss, and F. Loewus, eds. Wiley-Liss, New York. pp 163-172.
Boss, W. F. 1989. Plant phosphoinositide metabolism: A potential mechanism for signal transduction. In: Second Messengers in Plant Growth and Development. W.F. Boss and D. J. Morré, eds. Alan R. Liss, New York. pp. 29-56.
Dengler, L.A., M. Rincón, and W.F. Boss. NBD‑PC: A Tool to Study Endocytosis in Plant Protoplasts. In: Cell‑Free Analysis of Membrane Traffic. D. J. Morré, K. E. Howell, G. M. W. Cook, W. H. Evans, eds. Alan R. Liss, New York. 1988.
Boss, W. F. and Wheeler, J. J. 1989. Strategies for Optimizing Cell Fusion. In: Biotechnology Vol 7b. Verlagsgesellschaft, West Germany, pp 91-105.
Boss, W. F. 1987. Fusogenic Carrot Protoplasts: A Natural System for Studying Cell Fusion. In: Cell Fusion. A. Sowers, ed. Plenum, New York pp. 145-166.
Boss, W. F. and H. D. Grimes. 1985. Dynamics of Calcium‑induced Fusion of Fusogenic Carrot Protoplasts. In Beltsville Symposia on Agricultural Research IX. Frontiers of Membrane Research in Agriculture. J. St. John, P. Jackson, and E. Berlin, eds. Rowman & Allenhead Publishers, New Jersey. pp 63-68.
Heck, W.A., W.F. Boss. U. Blum, A.S. Heagle, R.A. Linthurst, R.A. Reinert, J.F. Reynolds, H.H. Rogers. 1984. Perspectives of Air Pollution Research on Plants. Reviews of Environmental Toxicology. Vol. 1, pp 173-234.