Toxicity of plant essential oil vapours to aphid pests and their coccinellid predators

The comparative toxicity of five essential oil vapours was tested against four aphid species, the black bean aphid Aphis fabae, the pea aphid Acyrthosiphon pisum, the chrysanthemum aphid Macrosiphoniella sanborni, the green peach aphid Myzus persicae and on two of the most common coccinellid predators, the seven-spotted ladybird Coccinella septempunctata and the two-spotted ladybird Adalia bipunctata. All essential oils were highly toxic to the aphid species tested with LC₅₀ and LC₉₉ values ranging between 0.17 and 1.92 and 0.44 and 4.83 µL/L air, respectively, depending on the aphid species and on the essential oil. Coccinellid predators were also highly susceptible to the essential oil vapours and the selective toxicity ratio varied depending on aphid species, coccinellid predator and essential oil. The possibilities for the utililization of essential oils as aphicides, especially in IPM programmes in glasshouses are discussed with regard to the present findings.     

Interaction of aminoadamantane derivatives with the influenza A virus M2 channel-Docking using a pore blocking model

Interaction of aminoadamantanes with the influenza A virus M2 proton channel was analyzed by docking simulations of a series of synthetic aminoadamantane derivatives, of differing binding affinity, into the crystal structure of the transmembrane (M2TM) pore. The pore blocking model tested in the ‘gas phase’ describes qualitatively the changes on the relative binding affinities of the compounds (although a series of highly hydrophobic ligands which seem to have little capacity for different specific interactions with their receptor). The docking calculations predicted poses in which the adamantane ring is surrounded mainly by the alkyl side chains of Val27 or Ala30 and the ligand’s amino group is generally hydrogen bonded with hydroxyls of Ser31 or carbonyls of Val27 or carbonyls of Ala30, the former (Ser31) being the most stable and most frequently observed. The binding of the ligand is a compromise between hydrogen bonding ability, which is elevated by a primary amino group, and apolar interactions, which are increased by the ability of the lipophilic moiety to adequately fill a hydrophobic pocket within the M2TM pore. A delicate balance of these hydrophobic contributions is required for optimal interaction.     

Nutrient- and density-dependent effects in a producer-consumer model

A class of models of a nutrient-producer-consumer community is studied analytically and numerically. The analytical study focuses upon the role of total system nutrient and consumer density dependence in governing system behavior and especially, on the persistence and extinction of the population. The numerical study demonstrates that the relationship between consumer density dependence, total system nutrient, and dynamic system behavior can be complicated. Features of the model system include behavior determined solely by total system nutrient, behavior where the relationship between total system nutrient and density dependence governs system dynamics, and behavior where nutrient enrichment or deplation cannot modify ultimate system structure. A conclusion, robust for the model consumer density dependent formulation, indicates that, in the case of ample total nutrient, persistence of the community is independent of consumer density dependence.     

19F NMR detection of the complex between amantadine and the receptor portion of the influenza A M2 ion channel in DPC micelles

(19)F NMR probes were used to follow interactions between ligands in the aminoadamantane series, amantadine (Am) 1 and 3-F-Am 2, and the 5-F-Trp20 transmembrane fragment of the influenza A M2 proton channel (F-M2TM 3) in dodecylphosphocholine micelles over the pH range 5-8. Above pH 7, when the peptide adopts a tetrameric state that is able to bind channel blocking ligands, (19)F-Trp signals from both the free and bound states of the M2TM tetramer are resolved. This differentiation of bound and unbound states of the M2TM receptor by (19)F NMR may provide a system for SAR studies.     

Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium-binding moieties

To confer bone-binding properties to proteins and other biological agents that lack specific targeting capacity, model peptide-based molecules were synthesized containing poly(aspartic acid), poly(glutamic acid), or a bisphosphonate (pamidronate). These motifs have well-documented affinities to hydroxyapatite, a property desirable for the targeting of molecules to bone for drug delivery and tissue engineering applications. Model peptides of increasing molecular mass (5-33 amino acids) were directly conjugated to eight aspartic acids (Asp8), eight glutamic acids (Glu8), or pamidronate, purified by high-performance liquid chromatography, and characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy. The modified peptides were incubated with hydroxyapatite in phosphate-buffered saline at physiological conditions over 24 h. This study revealed a significant amount (>90%) of conjugated peptides adsorbed to the hydroxyapatite as compared to unmodified peptides (<5%). It was found that while there were significant differences between the different hydroxyapatite-binding and control groups for all time points, the size of the peptide had no statistical effect on peptide-hydroxyapatite binding. These results demonstrate that bisphosphonate and oligopeptide conjugates hold great promise for the development of new bioactive molecules for bone-specific applications.     

Complex formation of bovine serum albumin with a poly(ethylene glycol) lipid conjugate

In this work, we report the formation of complexes by self-assembly of bovine serum albumin (BSA) with a poly(ethylene glycol) lipid conjugate (PEG2000-PE) in phosphate saline buffer solution (pH 7.4). Three different sets of samples have been studied. The BSA concentration remained fixed (1, 0.01, or 0.001 wt % BSA) within each set of samples, while the PEG2000-PE concentration was varied. Dynamic light scattering (DLS), rheology, and small-angle X-ray scattering (SAXS) were used to study samples with 1 wt % BSA. DLS showed that BSA/PEG2000-PE aggregates have a size intermediate between a BSA monomer and a PEG2000-PE micelle. Rheology suggested that BSA/PEG2000-PE complexes might be surrounded by a relatively compact PEG-lipid shell, while SAXS results showed that depletion forces do not take an important role in the stabilization of the complexes. Samples containing 0.01 wt % BSA were studied by circular dichroism (CD) and ultraviolet fluorescence spectroscopy (UV). UV results showed that at low concentrations of PEG-lipid, PEG2000-PE binds to tryptophan (Trp) groups in BSA, while at high concentrations of PEG-lipid the Trp groups are exposed to water. CD results showed that changes in Trp environment take place with a minimal variation of the BSA secondary structure elements. Finally, samples containing 0.001 wt % BSA were studied by zeta-potential experiments. Results showed that steric interactions might play an important role in the stabilization of the BSA/PEG2000-PE complexes.     

Targeting the late component of the cardiac L-type Ca2+ current to suppress early afterdepolarizations

Early afterdepolarizations (EADs) associated with prolongation of the cardiac action potential (AP) can create heterogeneity of repolarization and premature extrasystoles, triggering focal and reentrant arrhythmias. Because the L-type Ca²⁺ current (I_Ca,L) plays a key role in both AP prolongation and EAD formation, L-type Ca²⁺ channels (LTCCs) represent a promising therapeutic target to normalize AP duration (APD) and suppress EADs and their arrhythmogenic consequences. We used the dynamic-clamp technique to systematically explore how the biophysical properties of LTCCs could be modified to normalize APD and suppress EADs without impairing excitation–contraction coupling. Isolated rabbit ventricular myocytes were first exposed to H₂O₂ or moderate hypokalemia to induce EADs, after which their endogenous I_Ca,L was replaced by a virtual I_Ca,L with tunable parameters, in dynamic-clamp mode. We probed the sensitivity of EADs to changes in the (a) amplitude of the noninactivating pedestal current; (b) slope of voltage-dependent activation; (c) slope of voltage-dependent inactivation; (d) time constant of voltage-dependent activation; and (e) time constant of voltage-dependent inactivation. We found that reducing the amplitude of the noninactivating pedestal component of I_Ca,L effectively suppressed both H₂O₂- and hypokalemia-induced EADs and restored APD. These results, together with our previous work, demonstrate the potential of this hybrid experimental–computational approach to guide drug discovery or gene therapy strategies by identifying and targeting selective properties of LTCC.     

Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

Objectives  

It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS). However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH.