On the intraneural state of acetylcholine

Zusammenfassung Durch differenzierende Zentrifugierung von homogenisierten Organen wurde neuerdings nachgewiesen, dass die stark wirksamen, körpereigenen Amine Histamin, Adrenalin und Noradrenalin in Partikeln enthalten sind, die offenbar von halbdurchgängigen Membranen umgeben sind. Reagenzglasbefunde machen es ferner wahrscheinlich, dass diese Amine mit Phosphorlipoiden wasserunlösliche Komplexe bilden. Es sind bereits Anhaltspunkte dafür vorhanden, dass das in nervösen Organen vorhandene Acetylcholin sich den anderen Aminen analog verhält. Sollte sich durch künftige Versuche, für deren Durchführung gewisse Vorschläge gemacht werden, diese Annahme als richtig erweisen, so wäre die Unfähigkeit des Acetylcholins, in ruhenden Organen zu diffundieren, und damit seine Inaktivität und sein Schutz gegen die Esterasewirkung erklärt.

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In honor of Prof.Fritz Verzár on his seventieth birthday.     

The breakdown of continuum models for mechanical contacts

Forces acting within the area of atomic contact between surfaces play a central role in friction and adhesion. Such forces are traditionally calculated using continuum contact mechanics, which is known to break down as the contact radius approaches atomic dimensions. Yet contact mechanics is being applied at ever smaller lengths, driven by interest in shrinking devices to nanometre scales, creating nanostructured materials with optimized mechanical properties, and understanding the molecular origins of macroscopic friction and adhesion. Here we use molecular simulations to test the limits of contact mechanics under ideal conditions. Our findings indicate that atomic discreteness within the bulk of the solids does not have a significant effect, but that the atomic-scale surface roughness that is always produced by discrete atoms leads to dramatic deviations from continuum theory. Contact areas and stresses may be changed by a factor of two, whereas friction and lateral contact stiffness change by an order of magnitude. These variations are likely to affect continuum predictions for many macroscopic rough surfaces, where studies show that the total contact area is broken up into many separate regions with very small mean radius.     

Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.