Integrated model of farm parents’ decision-making process for bringing children into the farm work environment.

<p>Integrated model of farm parents’ decision-making process for bringing children into the farm work environment.</p

Balance scale model of the risks and benefits of bringing children into the farm work environment.

<p>Balance scale model of the risks and benefits of bringing children into the farm work environment.</p

Risk-perception ‘lens’ model of factors influencing farm parents’ decision to bring children into the farm work environment.

<p>Risk-perception ‘lens’ model of factors influencing farm parents’ decision to bring children into the farm work environment.</p

Participant demographics for semi-structured telephone interview of farm parents.

<p>Participant demographics for semi-structured telephone interview of farm parents.</p

α‑Conotoxin Dendrimers Have Enhanced Potency and Selectivity for Homomeric Nicotinic Acetylcholine Receptors

Covalently attached peptide dendrimers can enhance binding affinity and functional activity. Homogenous di- and tetravalent dendrimers incorporating the α7-nicotinic receptor blocker α-conotoxin ImI (α-ImI) with polyethylene glycol spacers were designed and synthesized via a copper-catalyzed azide–alkyne cycloaddition of azide-modified α-ImI to an alkyne-modified polylysine dendron. NMR and CD structural analysis confirmed that each α-ImI moiety in the dendrimers had the same 3D structure as native α-ImI. The binding of the α-ImI dendrimers to binding protein Ac-AChBP was measured by surface plasmon resonance and revealed enhanced affinity. Quantitative electrophysiology showed that α-ImI dendrimers had ∼100-fold enhanced potency at hα7 nAChRs (IC₅₀ = 4 nM) compared to native α-ImI (IC₅₀ = 440 nM). In contrast, no significant potency enhancement was observed at heteromeric hα3β2 and hα9α10 nAChRs. These findings indicate that multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic ion channels