Muscimol and some aza analogues: molecular orbital calculations relating to their potency as GABA mimetics

Ab initio molecular orbital calculations have been carried out on muscimol (1) and on two aza analogues, 5-aminomethylpyrazol-3-one (2) and 5-aminomethyl-1,2,4-triazol-3-one (3). Fully ionized species were studied in each case including the tautomeric forms of (2) and (3). The calculations reveal that the more stable tautomeric forms of (2) and (3) resemble muscimol in having a low energy barrier to rotation of the aminomethyl group (2–4 kcal mol^?1) but differ substantially from muscimol in the electronic character of the heterocyclic ring. The change in π-electron distribution in the more stable tautomers of (2) and (3) compared with muscimol is summarized by the dipole moment decrease (1) 7·75 au, (2) 6·62 au, (3) 5·81 au. In addition, the frontier molecular orbitals show analogous differences. On the other hand, the less stable tautomers of (2) and (3) are similar to muscimol in π-electron distribution and frontier orbitals, but have a high energy barrier to rotation of the aminomethyl group (11–14 kcal mol^?1). The calculated properties of the molecules are related to the ability of the three compounds to displace [³H]-GABA from the postsynaptic receptors of human cerebellum and it is suggested that the dominant influence on biochemical activity is the π-electron distribution in the heterocyclic ring.     

Endogenous Human Brain Dynamics Recover Slowly Following Cognitive Effort

Background

In functional magnetic resonance imaging, the brain''s response to experimental manipulation is almost always assumed to be independent of endogenous oscillations. To test this, we addressed the possible interaction between cognitive task performance and endogenous fMRI oscillations in an experiment designed to answer two questions: 1) Does performance of a cognitively effortful task significantly change fractal scaling properties of fMRI time series compared to their values before task performance? 2) If so, can we relate the extent of task-related perturbation to the difficulty of the task?

Methodology/Principal Findings

Using a novel continuous acquisition “rest-task-rest” design, we found that endogenous dynamics tended to recover their pre-task parameter values relatively slowly, over the course of several minutes, following completion of one of two versions of the n-back working memory task and that the rate of recovery was slower following completion of the more demanding (n = 2) version of the task.

Conclusion/Significance

This result supports the model that endogenous low frequency oscillatory dynamics are relevant to the brain''s response to exogenous stimulation. Moreover, it suggests that large-scale neurocognitive systems measured using fMRI, like the heart and other physiological systems subjected to external demands for enhanced performance, can take a considerable period of time to return to a stable baseline state.     

Patterns of mitochondrial haplotype diversity in the invasive pest Epiphyas postvittana (Lepidoptera: Tortricidae)

The light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), is a horticultural pest of Australia and New Zealand that has more recently invaded Hawaii, Europe, and California. A 2,216-bp region of the mitochondrial genome containing the cytochrome oxidase I and II genes was sequenced from 752 individuals. Haplotype network analyses revealed a major split between a predominantly Western Australian clade and all other samples, suggestive of either a deep genetic divergence or a cryptic species. Nucleotide and haplotype diversity were highest in the country of origin, Australia, and in New Zealand populations, with evidence of haplotype sharing between New Zealand and Tasmania. Nucleotide and haplotype diversity were higher in California than within the British Isles or Hawaii. From the total of 96 haplotypes, seven were found in California, of which four were private. Within California, there have been at least two introductions; based on genetic diversity we were unable to assign a likely source for a single moth found and eradicated in Los Angeles in 2007; however, our data suggest it is unlikely that Hawaii and the British Isles are sources of the major E. postvittana population found throughout the rest of the state since 2006.     

Radiation biology and inherited sterility of light brown apple moth (Lepidoptera: Tortricidae): developing a sterile insect release program

The radiation biology of two geographically isolated populations of the light brown apple moth [Epiphyas postvittana (Walker)] was studied in Australia and New Zealand as an initiation of a SIT/F1 sterility program. Pharate and < or = 2 d pre-emergence pupae were exposed to increasing radiation doses up to a maximum dose of 300 Gy. Fertility and other life history parameters were measured in emerging adults (parental) and their progeny (F1-F3 adults). Parental fecundity was significantly affected by increasing irradiation dose in pharate pupae only. For both populations, parental egg fertility declined with increasing radiation. This was most pronounced for the irradiated parental females whose fertility declined at a higher rate than of irradiated males. At 250 Gy, females < or = 2 d preemergence pupae produced few larvae and no adults at F1. No larvae hatched from 250 Gy-irradiated female pharate pupae. At 300 Gy, males still had residual fertility of 2-5.5%, with pharate pupae being the more radio-sensitive. Radiation-induced deleterious inherited effects in offspring from irradiated males were expressed as increased developmental time in F1 larvae, a reduction in percent F1 female survival, decreased adult emergence and increased cumulative mortality over subsequent generations. Males irradiated at > or = 150 Gy produced few but highly sterile offspring at F1 and mortality was > 99% by F2 egg.     

Intrinsic curvature: a marker of millimeter-scale tangential cortico-cortical connectivity?

In this paper, we draw a link between cortical intrinsic curvature and the distributions of tangential connection lengths. We suggest that differential rates of surface expansion not only lead to intrinsic curvature of the cortical sheet, but also to differential inter-neuronal spacing. We propose that there follows a consequential change in the profile of neuronal connections: specifically an enhancement of the tendency towards proportionately more short connections. Thus, the degree of cortical intrinsic curvature may have implications for short-range connectivity.     

Optimizing biocontrol using phenological day degree models: the European earwig in pipfruit orchards

• 1 Phenological day degree models are often used as warning systems for the emergence of arthropod pests in agricultural crops or the occurrence of natural enemies of the pest species. In the present study, we report on a case study of the European earwig Forficula auricularia L., which is an important natural enemy in pipfruit orchards, and describe how such a day degree model can be used to avoid negative effects of crucial orchard management, such as spray applications and soil tillage. A precise timing of these interventions in relation to the phenology of natural enemies will enhance biocontrol.
• 2 Earwig population dynamics are characterized by single‐ and double‐brood populations, each with specific biological characteristics.
• 3 A day degree model capable of predicting the phenology of local earwig populations of both population types was developed. The model was checked for accuracy by comparing the first field observation dates of various life stages with predicted values using temperature data from the nearest weather station. In addition, variation in development time was assessed using field data.
• 4 The model was able to make predictions on a global scale. Although single‐ and double‐brood populations differ in phenology, the predictions of first appearance dates were similar. Variation in development time showed that single‐brood populations were more synchronized.
• 5 Our phenological model provides an accurate tool for predicting and simulating earwig population dynamics, as well as for enhancing the biocontrol of pests in pipfruit orchards.

     

Evidence of active or passive downwind dispersal in mark–release–recapture of moths

Modelling moth dispersal in relation to wind direction and strength could greatly enhance the role of pheromone traps in biosecurity and pest management applications. Anemotaxis theory, which describes moth behaviour in the presence of a pheromone plume and is used as a framework for such models. Currently, however, that theory includes only three components: upwind, zigzagging, and sideways casting behaviour. We test anemotaxis theory by analysing the data from a series of mark–release–recapture experiments where the wind direction was known and the insects were trapped using an irregular grid of pheromone traps. The trapping results provide evidence of a downwind component to the flight patterns of the released insects. This active or passive downwind dispersal is likely to be an appetitive behaviour, occurring prior to the elicitation of pheromone‐oriented flight patterns (pheromone anemotaxis). Given the potential for significant displacement during downwind dispersal, this component will have impact on final trap captures and should be considered when constructing moth dispersal models.     

The importance of the phospholipid bilayer and the length of the cholesterol molecule in membrane structure

The properties of mixtures of phosphatidylcholine and analogues of cholesterol bearing side chains of varying lengths were examined by a variety of methods. The incorporation of the analogues into sonicated liposomes and their effect on the rate of osmotic shrinking of multilamellar liposomes were determined. The ordering of a steroid spin label was studied in an oriented multibilayer system and the effect of the analogues on the phase transition of dipalmitoyl phosphatidylcholine monitored using the spin label TEMPO ($\text{2,2,6,6-}\text{tetramethylpiperidine}\text{-N-}\text{oxyl}$). Mixtures of analogues and phospholipid were also studied in monolayers.In all the bilayer systems studied cholesterol caused the greatest ‘rigidifying’ effect, the analogues with shorter or longer side chains being less effective. However, in the monolayer experiments the length of the sterol molecule was found to be much less critical. It is suggested that cholesterol is anchored in position in a phospholipid bilayer by virtue of the molecule being the precise length required to maximise interactions between neighbouring molecules without disturbing the bilayer structure.