Dynamical studies of peptide motifs in the Plasmodium falciparum circumsporozoite surface protein by restrained and unrestrained MD simulations

The immunodominant region on the circumsporozoite surface (CS) protein of the malaria parasite Plasmodium falciparum contains 37 repeated copies of a asparagine-alanine-asparagine-proline (NANP) motif NMR studies of linear synthetic peptides containing one, two or three repeat units provided evidence for nascent type I beta-turns within the NPNA cadence in aqueous solution. The beta-turns could be stabilised upon substituting proline for alpha-methylproline (p(Me)) in the dodecamer (NP(Me)NA)3, without loss of the ability to elicit antibodies cross-reactive with P. falciparum sporozoites. In this work, four 4 ns MD simulations of the dodecapeptide Acetyl-(NP(Me)NA)3, in water, using NOE distance restraints, using 3J-coupling constant restraints, using both these restraints and without restraints, were carried out to determine the conformations of this peptide in aqueous solution. An unrestrained MD simulation of the unmethylated Ac-(NPNA)3 peptide in water was also carried out to investigate the effect of the additional methyl groups on the structure and dynamics of the peptide. The application of NOE distance restraints and 3J-coupling constant restraints leads to contradictory results, probably due to different averaging time scales inherent to the measurement of these data, which exceed the 100 ps averaging applied in the simulations. The additional methyl groups lead to more compact structures, which display enhanced local fluctuations. The central tetrapeptide adopts a type I beta-turn, while the outer motifs display more conformational variability. The three motifs in the methylated dodecamer peptide, however, adopt frequently in the distance restrained MD simulation a compact structure such that the outer motifs appear to form a hydrophobic core by stacking of their two proline rings. This arrangement also suggests how a peptide containing multiple tandemly linked copies of a stable beta-turn NPNA motif might adopt a folded stem-like structure, which conceivably may be of biological relevance in the native CS protein.     

Cancer in Circumpolar Inuit. Background information for Alaska

We compared rates of feeding on human hosts for blood-engorged female Anopheles quadrimaculatus species A, B and C1 collected from daytime resting sites in Manatee Springs State Park, Levy County, Florida during 1992-1993. Quick-blot DNA probes were used to identify mosquito taxa and also the presence of human blood in the mosquito gut. In collections from a campground area, human blood-feeding rates differed significantly among mosquito species (10.7% [19 of 177], 0%, [0 of 62], and 1.2%, [4 of 327]), respectively for species A, B and C1). In collections from a woodland site (1 km from the campground), 1.5% (2 of 129) of the species B females had fed on humans, whereas none of 19 species A or 159 species C1 females had done so. Of the three species in this study area, species A appears the most likely to be a biting pest of humans and a vector of human malaria.     

The mechanism of stressor suppression of the contractile function and reactivity of aortic smooth muscle

Blockade of the NO synthesis did not change the stressor augmentation of the acetylcholine-induced endothelium-dependent relaxation. The immobilisation stress seems to suppress the contractile function and the reactivity of the aorta smooth muscle reactivity as the result of augmentation of the NO basal production in endotheliocytes.