A Structural Rationale for N-Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand-Gated Ion Channels

Bicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABA_A receptors and affects other pentameric ligand-gated ion channels including the glycine, nicotinic acetylcholine and 5-hydroxytryptamine type 3 receptors. We used a fluorescence-quenching assay and isothermal titration calorimetry to record low-micromolar dissociation constants for N-methylbicuculline interacting with acetylcholine-binding protein and an engineered version called glycine-binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 Å resolution crystal structure of the GBP:N-methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABA_A receptor–bicuculline interactions. N-methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand-gated ion channels in the CNS.     

A numerical investigation of hydrogen injection into noble gas working fluids

The thermodynamic efficiency of internal combustion engines is primarily dependent on the compression ratio and specific heat ratio of the working fluid. Due to a higher specific heat ratio, using a noble gas and oxygen instead of air can increase the thermal efficiency. The lack of nitrogen in the working fluid also eliminates NOx formation. In this study, the three-dimensional turbulent injection of hydrogen into a constant volume combustion chamber has been modeled and compared to mixtures of oxygen with nitrogen, argon, and xenon at different injection velocities. The results indicate that the hydrogen jet has a longer penetration length in nitrogen compared to argon and xenon. However, smaller penetration lengths lead to more complex jet shapes and larger cone angles. Combustion in a noble gas environment results in higher temperatures and OH radical concentrations, due in part to lower specific heats and the jet characteristics. Furthermore, mixedness is investigated using mean spatial variation and mean scalar dissipation. Hydrogen in argon shows a better mixing rate compared to nitrogen and xenon due to the higher diffusivity. The results indicate that reduction in mean spatial variation can lead to a shorter ignition delay.     

The Bacterial Quality of an Upland Stream

Faecal coliform concentrations were determined at stream and water inflow sampling sites within an upland catchment in North Derbyshire containing rough, semiimproved and improved pastures. The results indicated that, during its passage through the catchment, the faecal indicators of the stream increased, and this may constitute a health risk to cavers using a popular recreational cave into which the stream drains. The decline in streamwater quality suggests that a semipermanent store of bacteria existed in catchment soils, and hydrological processes operated to transfer bacteria from the land to the stream channel. Contrary to expectations, intra-catchment differences in the bacterial quality of water at inflow and stream sampling sites could not be related to the intensity of agricultural land use in adjacent areas. This is explained with reference to changes in the nature of hydrological transport pathways associated with the improvement of pastures.     

The 2 k — p Fractional Factorial Designs Part II.

“… … …. but that there turtle is an insect.”     

An absolute interval scale of order for point patterns

Human observers readily make judgements about the degree of order in planar arrangements of points (point patterns). Here, based on pairwise ranking of 20 point patterns by degree of order, we have been able to show that judgements of order are highly consistent across individuals and the dimension of order has an interval scale structure spanning roughly 10 just-notable-differences (jnd) between disorder and order. We describe a geometric algorithm that estimates order to an accuracy of half a jnd by quantifying the variability of the size and shape of spaces between points. The algorithm is 70% more accurate than the best available measures. By anchoring the output of the algorithm so that Poisson point processes score on average 0, perfect lattices score 10 and unit steps correspond closely to jnds, we construct an absolute interval scale of order. We demonstrate its utility in biology by using this scale to quantify order during the development of the pattern of bristles on the dorsal thorax of the fruit fly.     

Misery loves company: Mood-congruent emotional responding to music.

We examined emotional responding to music after mood induction. On each trial, listeners heard a 30-s music excerpt and rated how much they liked it, whether it sounded happy or sad, and how familiar it was. When the excerpts sounded unambiguously happy or sad (Experiment 1), the typical preference for happy-sounding music was eliminated after inducing a sad mood. When the excerpts sounded ambiguous with respect to happiness and sadness (Experiment 2), listeners perceived more sadness after inducing a sad mood. Sad moods had no influence on familiarity ratings (Experiments 1 and 2). These findings imply that “misery loves company.” Listeners in a sad mood fail to show the typical preference for happy-sounding music, and they perceive more sadness in music that is ambiguous with respect to mood. (PsycINFO Database Record (c) 2011 APA, all rights reserved)