Selective and Irreversible Inhibitors of Aphid Acetylcholinesterases: Steps Toward Human-Safe Insecticides

Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 µM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using β-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems

Should the Law Governing Maritime Areas in the Arctic Adapt to Changing Climatic Circumstances?

The legal regime of the Arctic maritime areas has for a long time remained on the backburner of international norm creating activities. This can primarily be explained by the inhospitable climate which created natural barriers for human activities and imposed limits on the usefulness of the available technology.At present, however, climate change seems to be responsible for a marked heating up, not only of the mere physical environment of the Arctic, but also of the political tensions concerning the exact legal regime to be applied in the region.This chapter provides a close examination of the present-day legal status of the Arctic. Since almost all territorial claims have been settled in the area, the present contribution will only focus on the Arctic water areas with a special emphasis on navigation. Starting from what seems to have finally become a generally accepted legal cornerstone for appreciating the legal status of these waters, namely the 1982 United Nations Convention on the Law of the Sea, the chapter will first examine how climate change impacts on this legal regime. Subsequently, the vulnerability as well as the adaptive capacity of the 1982 Convention will be examined. Before drawing some conclusions, ways and means will be looked at for this existing legal system to better meet the new challenges that climate change poses for Arctic waters