A Synthetic mirror image of kalata B1 reveals that cyclotide activity is independent of a protein receptor

Featuring a circular, knotted structure and diverse bioactivities, cyclotides are a fascinating family of peptides that have inspired applications in drug design. Most likely evolved to protect plants against pests and herbivores, cyclotides also exhibit anti-cancer, anti-HIV, and hemolytic activities. In all of these activities, cell membranes appear to play an important role. However, the question of whether the activity of cyclotides depends on the recognition of chiral receptors or is primarily modulated by the lipid-bilayer environment has remained unknown. To determine the importance of lipid membranes on the activity of the prototypic cyclotide, kalata B1, we synthesized its all-D enantiomer and assessed its bioactivities. After the all-D enantiomer had been confirmed by (1)H NMR to be the structural mirror image of the native kalata B1, it was tested for anti-HIV activity, cytotoxicity, and hemolytic properties. The all-D peptide is active in these assays, albeit with less efficiency; this reveals that kalata B1 does not require chiral recognition to be active. The lower activity than the native peptide correlates with a lower affinity for phospholipid bilayers in model membranes. These results exclude a chiral receptor mechanism and support the idea that interaction with phospholipid membranes plays a role in the activity of kalata B1. In addition, studies with mixtures of L and D enantiomers of kalata B1 suggested that biological activity depends on peptide oligomerization at the membrane surface, which determines affinity for membranes by modulating the association-dissociation equilibrium.     

Comparison of New and Legacy TATBs

Two newly synthesized versions of the insensitive high explosive (IHE) 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) were compared to two legacy explosives currently used by the Department of Energy. Except for thermal analysis, small-scale safety tests could not distinguish between the different synthetic routes. Morphologies of new TATBs were less faceted and more spherical. The particle size distribution of one new material was similar to legacy TATBs, but the other was very fine. Densities and submicron structure of the new TATBs were also significantly different from the legacy explosives and the densities of pressed pellets were lower. Recrystallization of both new TATBs from sulfolane produced nearly hexagonal platelets with improved density and thermal stability.     

Maintaining design intent for aircraft manufacture

Design and manufacture of aircraft requires deep multi-disciplinary understanding of system behaviour. The intention of the designer can get lost due to the many changes occurring to the product and the inability of the methods and tools used to capture it. Systems engineering and optimisation tools underpin industrial approaches to design, but are not without issue. The challenge is to find a route from concept to manufacture which enables designers to maintain their original intent. The novelty in this work is that the parameterisation used to build the CAD model reflects the manufacturing capability, ensuring design intent is maintained from concept to manufacture.     

Steam reforming of ethanol over Co3O4–Fe2O3 mixed oxides

Co₃O₄, Fe₂O₃ and a mixture of the two oxides Co–Fe (molar ratio of Co₃O₄/Fe₂O₃ = 0.67 and atomic ratio of Co/Fe = 1) were prepared by the calcination of cobalt oxalate and/or iron oxalate salts at 500 °C for 2 h in static air using water as a solvent/dispersing agent. The catalysts were studied in the steam reforming of ethanol to investigate the effect of the partial substitution of Co₃O₄ with Fe₂O₃ on the catalytic behaviour. The reforming activity over Fe₂O₃, while initially high, underwent fast deactivation. In comparison, over the Co–Fe catalyst both the H₂ yield and stability were higher than that found over the pure Co₃O₄ or Fe₂O₃ catalysts. DRIFTS-MS studies under the reaction feed highlighted that the Co–Fe catalyst had increased amounts of adsorbed OH/water; similar to Fe₂O₃. Increasing the amount of reactive species (water/OH species) adsorbed on the Co–Fe catalyst surface is proposed to facilitate the steam reforming reaction rather than decomposition reactions reducing by-product formation and providing a higher H₂ yield.     

Task and sex modulate the brain response to emotional incongruity in Asian listeners.

In order to recognize banter or sarcasm in social interactions, listeners must integrate verbal and vocal emotional expressions. Here, we investigated event-related potential correlates of this integration in Asian listeners. We presented emotional words spoken with congruous or incongruous emotional prosody. When listeners classified word meaning as positive or negative and ignored prosody, incongruous trials elicited a larger late positivity than congruous trials in women but not in men. Sex differences were absent when listeners evaluated the congruence between word meaning and emotional prosody. The similarity of these results to those obtained in Western listeners suggests that sex differences in emotional speech processing depend on attentional focus and may reflect culturally independent mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.

The present study examined the effects of lesions of the central nucleus of the amygdala (CeA) on the acquisition of a new response with conditioned reinforcement (CR) and its potentiation by intra-accumbens infusions of d-amphetamine (1, 3, 10, and 20 μg/μl). Rats were trained to associate a light-plus-noise compound stimulus with the availability of a sucrose solution before receiving both bilateral ibotenic acid lesions of the CeA and cannulas implanted above the nucleus accumbens. Lesions of the central nucleus did not impair the performance of positively reinforced discriminated approach, nor did they impair the acquisition of a new response with conditioned reinforcement. However, the potentiation of responding with CR following intra-accumbens amphetamine was blocked in lesioned animals. These results are discussed in terms of the possible interactions between associative mechanisms in the amygdala and the mesolimbic dopamine projection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characteristics and outcome of anti-glomerular basement membrane disease: a single-center experience

The relative virulence and avirulence of Mycobacterium tuberculosis strains H37Rv and H37Ra were previously defined using animal infection models. To investigate host species' specificity of mycobacterial virulence, growth of the 2 M. tuberculosis strains in human monocyte-derived macrophages in vitro was studied. Mycobacterial growth was evaluated by acid-fast staining, electron microscopy, and colony-forming units (cfu) assay. As expected, the 2 strains demonstrated significantly different growth rates in mouse macrophages in vitro (53 h for H37Rv, 370 h for H37Ra). In marked contrast, in human macrophages the average division times of the strains were nearly equal (80 h for H37Rv and 76 h for H37Ra by cfu measurement, and 96 h for H37Rv and 104 h for H37Ra by acid-fast staining). These findings indicate that observations of mycobacterial virulence in murine systems may not necessarily translate to the human system, in which different mechanisms to control mycobacterial growth may be expressed.