Presenting Science Concisely by Kirchoff Bruce;Wagner Jon; & Jon Wagner

Author:Kirchoff, Bruce;Wagner, Jon; & Jon Wagner
Language: eng
Format: epub
Publisher: CAB International

Five-act structure

Act 1: current state of knowledge

a. Contact with Dendrocnide plants causes excruciating long-lasting pain.

b. The causative agent may be moroidin.

Act 2: conflicting evidence; new hypothesis

a. BUT:D. excelsa trichomes lack moroidin; purified extracts of moroidin do not produce the same long-lasting effects as the stings; injection of trichome extract purified to exclude moroidin still produced the symptoms of a sting (conflicting evidence).

b. Other pharmacologically active compounds are responsible for the stings (new hypothesis).

Act 3: first presentation of results

a. A late-eluting fraction of trichome extracts from D. excelsa elicits similar responses as the crude trichome extract.

b. Mass spectrometry of this fraction shows the presence of miniproteins stabilized by disulfide bonds.

c. BUT: Are these peptides responsible for the stings?

d. Synthetic versions of the peptides are synthesized.

e. Animal experiments with the synthetic versions reproduce the symptoms of a Dendrocnide sting.

Act 4: problems and their solution

a. BUT: How do the miniproteins function to cause the stings?

b. Fluorescence Ca2+ microscopy shows that Ca2+ influx occurs in neurons but not in non-excitable cells exposed to the peptides.

c. Patch-clamp electrophysiology confirms that the peptides work directly on NaV channels.

d. BUT: Can we be sure that the miniproteins occur in the trichomes?

e. MALDI-IMS demonstrates that compounds of the proper molecular weight localize specifically to the trichomes.

Act 5: conclusions

a. The causative agents of Dendrocnide stings are neurotoxins similar to those found in spider and cone snail venom.

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