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Botulinum Toxin
References
 

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References quick links:
Books

Video and Images
Literature
(** articles that are particularly useful for students)
Useful Sites / Journals
(All articles and archives are free)

Books

Alberts, B. et al. (2003). Essential Cell Biology, Second Edition. Garland Publishing. New York, NY. A comprehensive text for introductory level biology students or non-majors. This text also offers thought questions at the end of each chapter. This text contains a glossary and many ancillary materials.

Alberts, B. et al. (2002). Molecular Biology of the Cell, Fourth Edition. Garland Publishing. New York, NY. A detailed and comprehensive text designed for science majors. This text contains a glossary and many ancillary materials.

Brin, M. F. (1997). Spasticity, Etiology, Evaluation, Management, and the Role of Botulinum Toxin Type A. John Wiley & Sons, Inc. 20: S146-S168. (http://www.wemove.org/pdf/spa_MNSc09.pdfPDF Document.)

Jahn, R. and H. Niemann (1994). "Molecular mechanisms of clostridial neurotoxins." In Molecular and Cell Biological Aspects of Gastroenteropancreatic Neuroendocrine Tumor Disease. Annals of the New York Academy of Sciences 733: 245-55.

Rensberger, B. (1996). Life Itself. Oxford University Press. New York, NY. A "coffee table" book written for the general public and strongly recommended for non-majors. This paperback book, complete with a glossary, does an excellent job of placing intricate cellular processes in context. The book is also an excellent resource for cell biology majors, reminding them to place things in context and to integrate what they have learned.

Suput, D. and R. Zorac (1994). Toxins and Exocytosis. Annals of the New York Academy of Sciences 710. This text is a collection of papers presented at the New York Academy of Sciences symposium on the topic.

Video and Images

Aesthetics

WB11News at Ten (2001). "Botox Injections." Five Nights to a Better You. This is a one minute clip of a man receiving a Botox injection from his dermatologist for wrinkle removal.

Bioterrorism and Immunity

Schindler L, Kerrigan D, Kelly J. Science Behind the News: Understanding the Immune System. This site has a graphics slide show of immune response and vaccine development.
(http://newscenter.cancer.gov/sciencebehind/immune/immune01.htm)

The Biological and Toxin Weapons Convention (BTWC) Main Page. This site reviews the 1972 convention which produced a treaty that prohibits the manufacture, stockpiling or dissemination of biological weapons for offensive tactics.
(http://projects.sipri.se/cbw/docs/bw-btwc-mainpage.html)

DiscoverySchool.com (1997). "Botulinum Toxin" excerpt from the Understanding Bacteria video [VHS].1/2 video Color 1 cass., 51 min. #717603. Cost $49.95. A two minute clip at the beginning reviews the trajectory of toxin use, from bioweapon to medicinal miracle. The clip is particularly interesting, because students see the personalities of two major scientists of the field, Schantz and Johnson, as they prepare a batch of botulinum toxin.
(http://school.discovery.com/lessonplans/programs/understanding-bacteria/q.html)

Public Broadcasting Service (2001). "Nova: Bioterror." aired on November 13, 2001. [VHS] ½ video Color 1 cass., 60 min. Cost $19.95. This video shadows three NYC journalists as they follow bioterrorism stories over the last decade. The video has a companion website that contains interviews with bioterror specialists, journalists, and scientists. The website also has short video clips and tutorials for vaccine development.
(http://www.pbs.org/wgbh/nova/bioterror.html)

Public Broadcasting Service (2001). "Nova: Bioterror Companion Website." This video shadows three NYC journalists as they follow bioterrorism stories over the last decade. The video has a companion website that contains interviews with bioterror specialists, journalists, and scientists. The website also has short video clips and tutorials for vaccine development.
(http://www.pbs.org/wgbh/nova/bioterror/)
For making vaccines, see
(http://www.pbs.org/wgbh/nova/bioterror/vaccines.htm)
For interviews, see
(http://www.pbs.org/wgbh/nova/bioterror/biowarriors.html)
For global statistics, see
(http://www.pbs.org/wgbh/nova/bioterror/global.htm)

Bolton, J. R. (2001). Transcript of Press Briefing by the Honorable John R. Bolton, Under Secretary of State for Arms Control and International Security, United States. Fifth Review Conference of the Biological Weapons Convention, Palais des Nations, Geneva, Switzerland, U.S. Mission Geneva. This site contains multiple videos of lectures and statements made in reference to the BWTC and the U.S. position.
(http://www.brad.ac.uk/acad/sbtwc/other/bw-info.htm)

C-Span Senate Appropriations Subcommittee on Bioterrorism (October 23, 2001). This three hour stretch of video allows students to see interactions between scientists, politicians and law enforcement. Senators Tom Harkin and Arlen Specter reprimand the CDC for its handling of the anthrax letters in fall of 2001 and ask some pointed questions about our preparedness for another bioterror attack. Richard Koplan, Director of the CDC presents an epidemiological account of the anthrax attacks and Anthony Fauci, NIH Director, presents his arguments for funding of basic research.

Pearson, G. S., M. R. Dando, et al. (2001). Review Conference Paper No. 4: 'The US Statement at the Fifth Review Conference: Compounding the Error in Rejecting the Composite Protocol. Fifth Review Conference of the Biological Weapons Convention, Palais des Nations, Geneva, Switzerland. This site carries a collection of papers that deconstruct the U.S. position on the Biological and Chemical Weapons Convention Treaty. There are video clips of policy analysts and their views on the subject.
(http://www.brad.ac.uk/acad/sbtwc)
For Graham S. Pearson, David Atwood and Jenni Rissanen, see
(http://www.brad.ac.uk/acad/sbtwc/other/bw-info.htm)
For Jenni Rissanen, which is the the most informative clip, see (http://www.brad.ac.uk/acad/sbtwc/other/video/jenni56k.ramMovie.)
For Graham S. Pearson, see
(http://www.brad.ac.uk/acad/sbtwc/other/video/brightep22.ramMovie.)
For David Atwood, see
(http://www.brad.ac.uk/acad/sbtwc/other/video/davida56k.ramMovie.)

Cell Biology

Walter, P. and J. Theriot (2002). "Cell Biology Interactive." CD-ROM accompanying Alberts, B. et al. (2002) Molecular Biology of the Cell, Fourth Edition. The disk contains three video clips of intracellular trafficking and molecular structures. See 3.2 secretory pathway,13.3. Exoctytotic Transport,13.4 Endosome Fusion, 3.1 alpha helix, 3.2 Beta sheet, 3.11Safe crackers, and 7.2 Zinc Domain.

"Endocytosis." As part of the Interactive Concepts in Biology Version 3.0 CD-ROM accompanying Starr, et al. (2001) Biology: The Unity and Diversity of Life, Ninth Edition. Brookscole. Belmont, CA.

WEMOVE (2002). "Botulinum Toxin Type A Mechanism of Action." Video of BoNT/A binding, internalization, and cleavage of SNAP-25 and subsequent block of acetylcholine release and sprouting.
(http://www.mdvu.org/multimedia/videoclips/btx_moa.html)

Terry T. (2000). "Botulinum Toxin Mechanism of Action" as found in Biology 102: Lecture Notes: The Nervous System. University of Connecticut. November 13, 2000.
(http://www.microvet.arizona.edu/
Courses/MIC420/lecture_notes/clostri
dia/clostridia_neurotox/movie
/botulinum_movie.html
)

NIH. (2004) "The Brain: Understanding Neurobiology Through the study of Addiction, Lesson 2, Neurons, Brain Chemistry, Neurotransmission."
(http://science.education.nih.gov/supplements/nih2/addiction /activities/lesson2_neurotransmission.htm)

Allergan (2002). "Mechanism of BOTOX Action." Botulinum toxin action depicted in images.
(http://www.botox.com/site/professionals/ product_info/mechanism_of_action.asp)

Therapeutics

Public Broadcasting Service. (1993). "The Secret of Life #6: Cell Wars." [VHS 741]. 1/2 video Color 1 cass., 60 min. Looks at a powerful search-and-destroy mechanism that can defeat almost any invader-the immune system. When the immune system fails, vaccines can sometimes intervene. Gene technology offers the hope of vastly extending the ability to tailor vaccines to such incurable diseases as AIDS.

Public Broadcasting Service.(1993)."Secret of Life, #4: Conquering Cancer." [VHS 740]. 1/2 video Color 1 cass., 60 min. Probes the new understanding of the molecular machinery that causes cells to turn cancerous. The search for treatments for some types of cancer, such as inheritable breast cancer, has become a high-stakes hunt for a type of gene that is prone to become malignant. Once identified, such "oncogenes" are expected to point the way to cures.

Literature (** articles that are particularly useful for students)

Aesthetics

Altman, L. (March 10, 1998). Botulinum Toxin's Promise as Drug May Rival Its Potential as Weapon. New York Times. New York, N.Y.: F.7.

Avery, S. (2002). "Maker of Botox awaits FDA approval to market toxin for use in smoothing out wrinkles." The Detroit News April 2.**
(http://detnews.com/2002/health/0204/06/-455289.htm)

Handy , B. (1998). "That Deadpan Look." Time. 152: 72.

Hayt, E. (May 17, 1998). "Now at a Gym: Botox Injections." New York Times. New York, NY: 9.5.

Kuczynski, A. (February 2, 2002). "In Quest for Wrinkle-Free Future, Frown Becomes Thing of the Past." New York Times New York: A.1.**
(http://www.globalaging.org/health/us/wrinklefreefuture.htm)

Mead, R. (December 18, 2000)." The End of Sweat." The New Yorker 44.

Noonan, D. and J. Adler (May 13, 2002). "Botox Boom." Newsweek: 50-58.**

Young, A. (September 2001). " Botox or Bust." Departures.
(http://www.departures.com/he/he_0901_botox.html)

Bioterror

AAAS (2002). "Spotlight on Bioterrorism" Science and Technology in Congress: 3, 7.** This site reviews the current federal spending for biowarfare defense.
(http://www.aaas.org/spp/cstc/stc/stc02/02-02/bio.htm)

Arnon, S. S., R. Schechter, et al. (2001). "Botulinum toxin as a biological weapon: medical and public health management." JAMA 285(8): 1059-70.** This paper reviews the threat of botulinum toxin as a bioweapon and has excellent figures.
(http://jama.ama-assn.org/cgi/content/full/285/8/1059l)

Beardsley, T. (1999). "Facing an Ill Wind." Scientific American 280(4): 19-20.**
(http://www.sciam.com/article.cfm?articleID=0002F34D-5C49-1C70-84A9809EC588EF21)

Black, H. (2001). "Diagnosing Bioterrorism: Applying New Technologies." The Scientist 15(15): 8.
(http://www.the-scientist.com/yr2001/jul/black_p8_010723.html)

Bolton, J. R. (2001). Transcript of Press Briefing by the Honorable John R. Bolton, Under Secretary of State for Arms Control and International Security, United States. Fifth Review Conference of the Biological Weapons Convention, Palais des Nations, Geneva, Switzerland, U.S. Mission Geneva.**
(http://www.usmission.ch/press2001/1911bolton.htm)
and
(http://www.us-mission.ch/press2001/1119boltonpress.htm)

Cohen, J. and E. Marshall (2001). "Vaccines for Biodefense: A System in Distress." Science 294: 498-501.
(http://www.ph.ucla.edu/epi/bioter/vaccinesfordefense.html)

Pearson, G. S., M. R. Dando, et al. (2001). Review Conference Paper No. 4: 'The US Statement at the Fifth Review Conference: Compounding the Error in Rejecting the Composite Protocol'. Fifth Review Conference of the Biological Weapons Convention, Palais des Nations, Geneva, Switzerland.
(http://www.brad.ac.uk/acad/sbtwc/)

SIPRI, V., and ISN (2001). "Iraq: Biological Weapons Capability." Educational Module on Chemical & Biological Weapons (non)-Proliferation, Iraq: A case study.
(http://cbw.sipri.se/cbw/002060200.html)

Sotos, J. G. (2001). "Botulinum Toxin in Biowarfare."JAMA 285(21): 2716.**
(http://jama.ama-assn.org/cgi/content/full/285/21/2716)


Cell Communication

Environmental Agents Service-Department of Veteran Affairs. (2001). "Agent Orange General Information Brochure." (http://www.va.gov/agentorange/)

Centers for Disease Control (CDC). (1997). "Serum Dioxin in Vietnam-Era Veterans -- Preliminary Report." MMWR Weekly Report 36(28): 470-75. 2002. (http://www.cdc.gov/mmwr/pr
eview/mmwrhtml/00000939.htm
)

Poschet, J. F., J. C. Boucher, et al. (2001). "Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung." Proceedings of the National Academy of Sciences of the United States of America 98(24): 13972-7. 2002.
( http://www.pnas.org/cgi/content/f
ull/98/24/13972?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=
&fulltext=CFTR&searchid=1
020028776828_2687&stored_
search=&FIRSTINDEX=
0&volume=98&issue=24
)

Ramsey, I. "Cell Biology Resources for Educators" as part of the Internet School Library Media Center.
(http://falcon.jmu.edu/~ramseyil/cellbiology.htm)

Ridley, M. (1999). "Disease." Genome: The autobiography of a species in 23 chapters. New York, HarperCollins: 136-146.

RMIT University, D. o. M. L. S. (2001). "The ABO Blood Group System."
(http://www.life.rmit.edu.au/mls/subjects/abo/resources/directory.htm)

Scott, J. and T. Pawson (2000). Cell communication: The inside story. Scientific American. 282: 72-80. This site does not have the colorful figures, so obtain via campus databases.
(http://www.mshri.on.ca/pawson/publications/SciAm.pdfPDF Document.)

Exocytosis

Huttner, W. B. (1993). "Cell biology. Snappy exocytoxins." Nature 365(6442): 104-5.**

Ohara-Imaizumi, M., Y. Nakamichi, et al. (2002). "Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy: distinct behavior of granule motion in biphasic insulin release." The Journal of Biological Chemistry 277: 3805-3808.

Rothman, J. E. and G. Warren (1994). "Implications of the SNARE hypothesis for intracellular membrane topology and dynamics." Current Biology 4(3): 220-33.

Scales, S. J., J. B. Bock, et al. (2000). "The specifics of membrane fusion." Nature 407(6801): 144-6.**

Sollner, T., S. W. Whiteheart, et al. (1993). "SNAP receptors implicated in vesicle targeting and fusion." Nature 362(6418): 318-24.

Sudhof, T. C., P. De_Camilli, et al. (1993). "Membrane fusion machinery: insights from synaptic proteins." Cell 75(1): 1-4.**

Warren, G. (1993). "Cell biology. Bridging the gap." Nature 362(6418): 297-8.**

Host Cell Receptors for Botulinum

Bakry, N. M., Y. Kamata, et al. (1997). "Expression of botulinum toxin binding sites in Xenopus oocytes." Infection and Immunity 65(6): 2225-32.
(http://iai.asm.org/cgi/reprint/65/6/2225.pdfPDF Document.)

Geppert, M., B. T. Archer, et al. (1991). "Synaptotagmin II. A novel differentially distributed form of synaptotagmin." Journal of Biological Chemistry 266(21): 13548-52.
(http://www.jbc.org/cgi/reprint/266/21/13548)

Ginalski, K., C. Venclovas, et al. (2000). "Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site." Febs Letters 482(1-2): 119-24.
(http://www.elsevier.com/febs/120/18/39/index.htt)

Habermann, E. and F. Dreyer (1986). "Clostridial neurotoxins: handling and action at the cellular and molecular level." Current Topics in Microbiology and Immunology 129: 93-179.

Halpern, J. L. and E. A. Neale (1995). "Neurospecific binding, internalization, and retrograde transport." Current Topics in Microbiology and Immunology 195: 221-241.

Kozaki, S., Y. Kamata, et al. (1998). "Ganglioside GT1b as a complementary receptor component for Clostridium botulinum neurotoxins." Microbial Pathogenesis 25(2): 91-9.

Lacy, D. B. and R. C. Stevens (1998). "Unraveling the structures and modes of action of bacterial toxins." Current Opinion in Structural Biology 8(6): 778-84.

Lalli, G., J. Herreros, et al. (1999). "Functional characterisation of tetanus and botulinum neurotoxins binding domains." Journal of Cell Science 112 ( Pt 16): 2715-24.
(http://jcs.biologists.org/cgi/reprint/112/16/2715.pdfPDF Document.)

Li, L. and B. R. Singh (1998). "Isolation of synaptotagmin as a receptor for types A and E botulinum neurotoxin and analysis of their comparative binding using a new microtiter plate assay." Journal of Natural Toxins 7(3): 215-26.

Nishiki, T., Y. Kamata, et al. (1994). "Identification of protein receptor for Clostridium botulinum type B neurotoxin in rat brain synaptosomes." Journal of Biological Chemistry 269(14): 10498-503.
(http://www.jbc.org/cgi/reprint/269/14/10498.pdfPDF Document.)

Nishiki, T., Y. Tokuyama, et al. (1996). "The high-affinity binding of Clostridium botulinum type B neurotoxin to synaptotagmin II associated with gangliosides GT1b/GD1a." Febs Letters 378(3): 253-7.

Montecucco, C. (1986). "How do tetanus and botulinum toxins bind to neuronal membranes?" Trends in Biochem. Sci. 11: 315-317.

Swaminathan, S. and S. Eswaramoorthy (2000). "Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B." Nature Structural Biology 7(8): 693-9.

Inhibitors

Adler, M., J. D. Nicholson, et al. (1998). "Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity." Febs Letters 429(3): 234-8.
(http://www.elsevier.com/febs/93/17/17/main.pdfPDF Document.)

Adler, M., J. D. Nicholson, et al. (1999). "Evaluation of phosphoramidon and three synthetic phosphonates for inhibition of botulinum neurotoxin B catalytic activity." Journal of Applied Toxicology 19 Suppl 1: S5-S11.

Anne, C., F. Cornille, et al. (2001). "High-throughput fluorogenic assay for determination of botulinum type B neurotoxin protease activity." Analytical Biochemistry 291(2): 253-61.

Garcia, G. E., D. R. Moorad, et al. (1999). "Buforin I, a natural peptide, inhibits botulinum neurotoxin B activity in vitro." Journal of Applied Toxicology 19 Suppl 1: S19-22.** This entire supplement is on "Medical Countermeasures to Botulinum Toxins and Topical Skin Protectants Against Nerve and Vesicating Agents "
(http://www3.interscience.wiley.com/cgi-bin/issuetoc?ID=68501553)

Lacy, D. B., W. Tepp, et al. (1998). "Crystal structure of botulinum neurotoxin type A and implications for toxicity." Nature Structural Biology 5(10): 898-902.

Mullaney, B. P., M. G. Pallavicini, et al. (2001). "Epitope mapping of neutralizing botulinum neurotoxin A antibodies by phage display." Infection and Immunity 69(10): 6511-4.
(http://iai.asm.org/cgi/conten
t/full/69/10/6511?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=
&searchid=1020293482113_2792&stored_search=
&FIRSTINDEX=0&volume=69&firstpage=6511&journalcode=iai
)

Roques, B. P., C. Anne, et al. (2000). "Mechanism of action of clostridial neurotoxins and rational inhibitor design." Biology of the Cell 92(6): 445-7.

Satoh, E., T. Ishii, et al. (2001). "Black tea extract, thearubigin fraction, counteract the effects of botulinum neurotoxins in mice." British Journal of Pharmacology 132(4): 797-8.

Schmidt, J. J., R. G. Stafford, et al. (2001). "High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes a, b, d, and f." Analytical Biochemistry 296(1): 130-7.

Zdanovsky, A. G., N. V. Karassina, et al. (2001). "Peptide phage display library as source for inhibitors of clostridial neurotoxins." Journal of Protein Chemistry 20(1): 73-80.

Molecular Mechanisms

Binz, T., J. Blasi, et al. (1994). "Proteolysis of SNAP-25 by types E and A botulinal neurotoxins." Journal of Biological Chemistry 269(3): 1617-20.
(http://www.jbc.org/cgi/reprint/269/3/1617.pdfPDF Document.)

Blanes_Mira, C., C. Ibanez, et al. (2001). "Thermal stabilization of the catalytic domain of botulinum neurotoxin E by phosphorylation of a single tyrosine residue." Biochemistry 40(7): 2234-42.

Blasi, J., E. R. Chapman, et al. (1993). "Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25." Nature 365(6442): 160-3.

Blasi, J., E. R. Chapman, et al. (1993). "Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin." Embo Journal 12(12): 4821-8. **

Chen, Y. A., S. J. Scales, et al. (2001). "A discontinuous SNAP-25 C-terminal coil supports exocytosis." Journal of Biological Chemistry 276(30): 28503-8.
(http://www.jbc.org/cgi/content/f
ull/276/30/28503?maxtoshow=&HITS=10&hits=10&RESULTFORMAT
=&fulltext=coil&searchid=
1020293051483_7211&stored_search=&FIRSTINDEX=0&
volume=276&issue=30&journalcode=jbc
)

Chen, Y. A., S. J. Scales, et al. (2001). "Sequential SNARE assembly underlies priming and triggering of exocytosis." Neuron 30(1): 161-70.

Cutler, D. (1992). "Cell biology. Progress by poisoning." Nature 359(6398): 773. **

Fukuda, R., J. A. McNew, et al. (2000). "Functional architecture of an intracellular membrane t-SNARE." Nature 407(6801): 198-202.

Gerritson, V. B. (2002). "From Sausages to Wrinkles." Protein Spotlight Online(19).
(http://www.expasy.org/spotlight/articles/sptlt019.html)

Hayashi, T., H. McMahon, et al. (1994). "Synaptic vesicle membrane fusion complex: action of clostridial neurotoxins on assembly." Embo Journal 13(21): 5051-61.

Humeau, Y., F. Doussau, et al. (2000). "How botulinum and tetanus neurotoxins block neurotransmitter release." Biochimie 82(5): 427-46.**

Huttner, W. B. (1993). "Cell biology. Snappy exocytoxins." Nature 365(6442): 104-5.**

Johnson, E. A. (1999). "Clostridial toxins as therapeutic agents: benefits of nature's most toxic proteins." Annual Review of Microbiology 53: 551-75.**

Kalandakanond, S. and J. A. Coffield (2001). "Cleavage of SNAP-25 by Botulinum Toxin Type A Requires Receptor-Mediated Endocytosis, pH-Dependent Translocation, and Zinc." J Pharmacol Exp Ther 296(3): 980-986.
(http://jpet.aspetjournals.org/cgi/content/full/296/3/980)

Linial, M. (1995). "Bacterial neurotoxins--a thousand years later." Israel Journal of Medical Sciences 31(10): 591-5.**

McNew, J. A., F. Parlati, et al. (2000). "Compartmental specificity of cellular membrane fusion encoded in SNARE proteins." Nature 407(6801): 153-9.**
Montecucco, C. and G. Schiavo (1993). "Tetanus and botulism neurotoxins: a new group of zinc proteases." Trends in Biochemical Sciences 18(9): 324-7.**

Oblatt-Montal, M., M. Yamazaki, et al. (1995). "Fig 6. Computer generated model of the ion channel motif formed by BoTxATM."
(http://www.prosci.uci.edu/Articles/Vol4/issue8/5043/5043.html#fig6)

Pellizzari R, Rossetto O, Schiavo G, Montecucco C. (1999) "\Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences. 354(1381): 259-68.
(http://dandini.ingentaselect.com/vl=3271893/cl=11/nw=1/rpsv/
cw/rsl/09628436/v354n1381/s3/p259.idx
)

Schiavo, G., F. Benfenati, et al. (1992). "Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin." Nature 359(6398): 832-5.

Schiavo, G., M. Matteoli, et al. (2000). "Neurotoxins affecting neuroexocytosis." Physiological Reviews 80(2): 717-66.
(http://physrev.physiology.org/cgi/content/full/80/2/717)

Sollner, T., S. W. Whiteheart, et al. (1993). "SNAP receptors implicated in vesicle targeting and fusion." Nature 362(6418): 318-24.**

Sudhof, T. "Mechanism and Regulation of Neurotransmitter Release."
(http://www.hhmi.org/research/investigators/sudhof.html)

Sudhof, T. C. (1995). "The synaptic vesicle cycle: a cascade of protein-protein interactions." Nature 375(6533): 645-53.

Sudhof, T. C., P. De_Camilli, et al. (1993). "Membrane fusion machinery: insights from synaptic proteins." Cell 75(1): 1-4.

Terry T. (2000)."Botulinum Toxin Mechanism of Action" as found in Biology 102: Lecture Notes: The Nervous System. University of Connecticut. November 13, 2000.**
(http://www.microvet.arizona.edu
/Courses/MIC420/lecture_notes/clostridia/clostridia_neurotox/
movie/botulinum_movie.html
)

Walch_Solimena, C., J. Blasi, et al. (1995). "The t-SNAREs syntaxin 1 and SNAP-25 are present on organelles that participate in synaptic vesicle recycling." Journal of Cell Biology 128(4): 637-45.

Warren, G. (1993). "Cell biology. Bridging the gap." Nature 362(6418): 297-8.**

Structures of Botulinum and its Targets

Binz, T., J. Blasi, et al. (1994). "Proteolysis of SNAP-25 by types E and A botulinal neurotoxins." Journal of Biological Chemistry 269(3): 1617-20.
(http://www.jbc.org/cgi/reprint/269/3/1617.pdfPDF Document.)

Blanes_Mira, C., C. Ibanez, et al. (2001). "Thermal stabilization of the catalytic domain of botulinum neurotoxin E by phosphorylation of a single tyrosine residue." Biochemistry 40(7): 2234-42.

Bullough, P. A., F. M. Hughson, et al. (1994). "Structure of influenza haemagglutinin at the pH of membrane fusion." Nature 371(6492): 37-43.

Fukuda, R., J. A. McNew, et al. (2000). "Functional architecture of an intracellular membrane t-SNARE." Nature 407(6801): 198-202.

Ginalski, K., C. Venclovas, et al. (2000). "Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site." Febs Letters 482(1-2): 119-24.
(http://www.elsevier.com/febs/120/18/39/index.htt)

Hanson, M. A. and R. C. Stevens (2000). "Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution." Nature Structural Biology 7(8): 687-92.

Kargul, J., X. Gansel, et al. (2001). "Protein-binding partners of the tobacco syntaxin NtSyr1." Febs Letters 508(2): 253-8.

Lacy, D. B. and R. C. Stevens (1998). "Unraveling the structures and modes of action of bacterial toxins." Current Opinion in Structural Biology 8(6): 778-84.

Lacy, D. B., W. Tepp, et al. (1998). "Crystal structure of botulinum neurotoxin type A and implications for toxicity." Nature Structural Biology 5(10): 898-902.

Lalli, G., J. Herreros, et al. (1999). "Functional characterisation of tetanus and botulinum neurotoxins binding domains." Journal of Cell Science 112 ( Pt 16): 2715-24.
(http://jcs.biologists.org/cgi/reprint/112/16/2715.pdfPDF Document.)

Lawrence, E. (1998). "Getting to Grips With Botulinum Toxin."**
(http://www.nature.com/nsu/981029/981029-2.html)

Maksymowych, A. B. and L. L. Simpson (1998). "Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells." Journal of Biological Chemistry 273(34): 21950-7.
(http://www.jbc.org/cgi/content/full/273/34/21950?maxtoshow=&
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O'Connor, V. M., O. Shamotienko, et al. (1993). "On the structure of the 'synaptosecretosome'. Evidence for a neurexin/synaptotagmin/syntaxin/Ca2+ channel complex." Febs Letters 326(1-3): 255-60.

Parlati, F., J. A. McNew, et al. (2000). "Topological restriction of SNARE-dependent membrane fusion." Nature 407(6801): 194-8.

Rossetto, O., G. Schiavo, et al. (1994). "SNARE motif and neurotoxins." Nature 372(6505): 415-6.

Rupp, B. and B. Segelke (2001). "Questions about the structure of the botulinum neurotoxin B light chain in complex with a target peptide." Nature Structural Biology 8(8): 663-4.

Schiavo, G., M. Matteoli, et al. (2000). "Neurotoxins affecting neuroexocytosis." Physiological Reviews 80(2): 717-66.**
(http://physrev.physiology.org/cgi/content/full/80/2/717)

Umland, T. C., L. M. Wingert, et al. (1997). "Structure of the receptor binding fragment HC of tetanus neurotoxin." Nature Structural Biology 4(10): 788-92.

Weissenhorn, W., A. Dessen, et al. (1997). "Atomic structure of the ectodomain from HIV-1 gp41." Nature 387(6631): 426-30.

Wu, C. (1998). "Killer toxin's punch lies below the belt." Science News 154(14): 213.**

Therapeutic Uses for Botulinum Toxin

Abate, T. (December 12, 2000). Elan's Botulism-Based Anti-Spasm Drug Wins FDA OK. San Francisco Chronicle. San Francisco: C2.

Ballon, M. (September 25, 2000). The Cutting Edge: Focus on Technology; Allergan Chief Has Injected New Energy Into Once-Lagging Firm; Pharmaceuticals: Botox maker's stock, profit, sales have shot up in his 2 1/2-year tenure. Future success may be. Los Angeles Times. Los Angeles: C1.

Brin, M. F. (1997). "Botulinum Toxin: Chemistry, Pharmacology, Toxicity, and Immunology." Spasticity, Etiology, Evaluation, Management, and the Roleof Botulinum Toxin Type A. M. F. Brin, John Wiley & Sons, Inc. 20: S146-S168.**
(http://www.wemove.org/pdf/spa_MNSc09.pdfPDF Document.)

Chen, I. (1991). "Toxin to the Rescue." Science News 139(3): 42-43.**
FDA (2002). "FDA Talk Paper: FDA Approves Botox to Treat Frown Lines."
(http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01147.html)

Jankovic, J. and M. F. Brin (1997). "Botulinum Toxin: Historical Perspective and Potential New Indications." Spasticity, Etiology, Evaluation, Management, and the Role of Botulinum Toxin Type A. M. F. Brin, John Wiley & Sons, Inc. 20: S129-S145.**
(http://www.wemove.org/pdf/spa_MNSc08.pdfPDF Document.)

Johnson, E. A. (1999). "Clostridial toxins as therapeutic agents: benefits of nature's most toxic proteins." Annual Review of Microbiology 53: 551-75.**

Kirschner, J., S. Berweck, et al. (2001). "Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option." Journal of Neurology 248 Suppl 1: 28-30.

Pellizzari, R., O. Rossetto, et al. (1999). "Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354(1381): 259-68**
(http://dandini.ingentaselect.com/vl=3271893/cl=11/nw=1/rpsv/
cw/rsl/09628436/v354n1381/s3/p259.idx
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Petit, C. (October 15,1986). "Tragic Drug Cutoff for Sufferers of Mystery Eye Malady Charles Petit." San Francisco Chronicle. San Francisco: 2.

Schantz, E. J. and E. A. Johnson (1997). "Botulinum toxin: the story of its development for the treatment of human disease." Perspectives in Biology and Medicine 40(3): 317-27.**

Simpson, L. L. (2000). "Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs." Biochimie 82(9-10): 943-53.**

Simpson, D. M. (1997). "Clinical Trials of Botulinum Toxin in the Treatment of Spasticity." Spasticity, Etiology, Evaluation, Management, and the Role of Botulinum Toxin Type A. M. F. Brin, John Wiley & Sons, Inc. 20: S169-S175.**
(http://www.wemove.org/pdf/spa_MNSc10.pdfPDF Document.)

Simpson, L., N. Kiyatkin, et al. (1997). "Compositions and methods for systemic delivery of oral vaccines and therapeutic agents." Pharmcast.com. U.S.A., Thomas Jefferson University (Philadelphia, PA). 1997.**
(http://www.pharmcast.com/Patents/041800OG/6051239_Vaccines041800.htm)


Therapeutic Chimeras

Arora, N., R. Masood, et al. (1999). "Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells." Cancer Research 59(1): 183-8.

Azemar, M., M. Schmidt, et al. (2000). "Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo." International Journal of Cancer 86(2): 269-75.

Ciardiello, F. (2000). "Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents." Drugs 60 Suppl 1:25-32; discussion 41-2.

FDA (1995). "From Test Tube To Patient: New Drug Development in the United States." FDA Consumer January.
(http://www.fda.gov/fdac/special/newdrug/ndd_toc.html)

Hudson, P. J. (1998). "Recombinant antibody fragments." Current Opinion in Biotechnology 9(4): 395-402.

Hung, C. F., W. F. Cheng, et al. (2001). "Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen." Cancer Research 61(9): 3698-703.

Kiyatkin, N., A. B. Maksymowych, et al. (1997). "Induction of an immune response by oral administration of recombinant botulinum toxin." Infection and Immunity 65(11): 4586-91.
http://iai.asm.org/cgi/reprint/65/11/4586.pdf

Kreitman, R. J. (2000). "Immunotoxins." Expert Opinion in Pharmacotherapy 1(6): 1117-29. **

Lacy, D. B. and R. C. Stevens (1998). "Unraveling the structures and modes of action of bacterial toxins." Current Opinion in Structural Biology 8(6): 778-84.

Liu, S., T. H. Bugge, et al. (2001). "Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin." Journal of Biological Chemistry 276(21): 17976-84.
(http://www.jbc.org/cgi/content/full/
276/21/17976?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&
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Liu, S., S. Netzel_Arnett, et al. (2000). "Tumor cell-selective cytotoxicity of matrix metalloproteinase-activated anthrax toxin." Cancer Research 60(21): 6061-7.

Mendelsohn, J. and J. Baselga (2000). "The EGF receptor family as targets for cancer therapy." Oncogene 19(56): 6550-65.**

Pastan, I. and D. FitzGerald (1991). "Recombinant toxins for cancer treatment." Science 254(5035): 1173-7.**

Pecoul B, Chirac P, Trouiller P, Pinel J. (1999). "Access to essential drugs in poor countries: a lost battle?" JAMA 281(4):361-7.
http://www.accessmed-msf.org/prod/publications.asp?
scntid=3082001626242&contenttype=PARA&
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Simpson, L. L. (2000). "Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs." Biochimie 82(9-10): 943-53.

Yoon, J. M., S. H. Han, et al. (1999). "Cloning and cytotoxicity of fusion proteins of EGF and angiogenin." Life Sciences 64(16): 1435-45.

Vaccines for Botulism

Byrne, M. P. and L. A. Smith (2000). "Development of vaccines for prevention of botulism." Biochimie 82(9-10): 955-66.**

Cohen, J. and E. Marshall (2001). "Vaccines for Biodefense: A System in Distress." Science 294: 498-501.**
(http://www.ph.ucla.edu/epi/bioter/vaccinesfordefense.html)

Kiyatkin, N., A. B. Maksymowych, et al. (1997). "Induction of an immune response by oral administration of recombinant botulinum toxin." Infection and Immunity 65(11): 4586-91.
(http://iai.asm.org/cgi/reprint/65/11/4586.pdfPDF Document.)

Kreitman, R. J. (2000). "Immunotoxins." Expert Opinion in Pharmacotherapy 1(6): 1117-29.**

Lacy, D. B. and R. C. Stevens (1998). "Unraveling the structures and modes of action of bacterial toxins." Current Opinion in Structural Biology 8(6): 778-84.

Lee, J. S., P. Pushko, et al. (2001). "Candidate vaccine against botulinum neurotoxin serotype A derived from a Venezuelan equine encephalitis virus vector system." Infection and Immunity 69(9): 5709-15.
(http://iai.asm.org/cgi/content/full/69/9/5709?maxtoshow=&HITS=
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Mullaney, B. P., M. G. Pallavicini, et al. (2001). "Epitope mapping of neutralizing botulinum neurotoxin A antibodies by phage display." Infection and Immunity 69(10): 6511-4.
(http://iai.asm.org/cgi/content/full/69/10/6511?maxtoshow=&HITS=
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Roques, B. P., C. Anne, et al. (2000). "Mechanism of action of clostridial neurotoxins and rational inhibitor design." Biology of the Cell 92(6): 445-7.

Schmitt, C. K., K. C. Meysick, et al. (1999). "Bacterial toxins: friends or foes?" Emerging Infectious Diseases 5(2): 224-34.**
(http://www.cdc.gov/ncidod/eid/vol5no2/schmitt.htm)

Schmidt, J. J., R. G. Stafford, et al. (2001). "High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes a, b, d, and f." Analytical Biochemistry 296(1): 130-7.

Simpson, L., N. Kiyatkin, et al. (1997). Compositions and methods for systemic delivery of oral vaccines and therapeutic agents. Pharmcast.com. U.S.A., Thomas Jefferson University (Philadelphia, PA). 1997.
(http://www.pharmcast.com/Patents/041800OG/6051239_Vaccines041800.htm)

Simpson, L. L. (2000). "Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs." Biochimie 82 (9-10): 943-53.**

Wu, C. (1998). "Killer toxin's punch lies below the belt." Science News 154(14): 213.

Zdanovsky, A. G., N. V. Karassina, et al. (2001). "Peptide phage display library as source for inhibitors of clostridial neurotoxins." Journal of Protein Chemistry 20(1): 73-80.

Useful Sites / Journals (All articles and archives are free)

Flying Publisher. This site contains a list of all journals that provide full text freely over the internet. The site contains many useful journals, such as Journal of Biological Chemistry, Journal of Cell Biology, Journal of Cell Science, Biomed Central Cell Biology, Infection and Immunity, and others.
(http://www.freemedicaljournals.com/htm/english2.htm)

Highwire Press. This site contains a list of all journals that provide full text freely over the internet. The site contains many useful journals, such as Journal of Biological Chemistry, Journal of Cell Biology, Journal of Cell Science, Biomed Central Cell Biology, Infection and Immunity, and others.
(http://highwire.stanford.edu)

Science News Magazine. This weekly magazine publishes articles appropriate for undergraduates.
(http://www.sciencenews.org/)

Modern Drug Discovery Journal. This weekly journal publishes articles appropriate for undergraduates and is an American Chemical Society publication.
(http://pubs.acs.org/journals/mdd/)

The Scientist News Journal. This journal publishes articles appropriate for undergraduates and has interesting review articles.
(http://www.the-scientist.com/)





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