Molecular recycling within amyloid fibrils

Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.     

Décharge catalytique du proton en présence de séléno-cystine et de nickel

Summary It has been found that seleno-cystine, reduced to seleno-cysteine and bound in ligand form to nickel ion, produces catalytic hydrogen discharge in slight acid media. This discharge occurs in the region of a catalytic prewave located at more positive potentials (E_1/2=–1.14 V, S.C.E.) compared with the normal wave of H₃O+(E_1/2=–1,67 V, S.C.E.).     

Intermittent dislocation flow in viscoplastic deformation

The viscoplastic deformation (creep) of crystalline materials under constant stress involves the motion of a large number of interacting dislocations. Analytical methods and sophisticated 'dislocation dynamics' simulations have proved very effective in the study of dislocation patterning, and have led to macroscopic constitutive laws of plastic deformation. Yet, a statistical analysis of the dynamics of an assembly of interacting dislocations has not hitherto been performed. Here we report acoustic emission measurements on stressed ice single crystals, the results of which indicate that dislocations move in a scale-free intermittent fashion. This result is confirmed by numerical simulations of a model of interacting dislocations that successfully reproduces the main features of the experiment. We find that dislocations generate a slowly evolving configuration landscape which coexists with rapid collective rearrangements. These rearrangements involve a comparatively small fraction of the dislocations and lead to an intermittent behaviour of the net plastic response. This basic dynamical picture appears to be a generic feature in the deformation of many other materials. Moreover, it should provide a framework for discussing fundamental aspects of plasticity that goes beyond standard mean-field approaches that see plastic deformation as a smooth laminar flow.     

Active tactile exploration using a brain-machine-brain interface

Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses.     

Ocean-like water in the Jupiter-family comet 103P/Hartley 2

For decades, the source of Earth's volatiles, especially water with a deuterium-to-hydrogen ratio (D/H) of (1.558?±?0.001)?×?10(-4), has been a subject of debate. The similarity of Earth's bulk composition to that of meteorites known as enstatite chondrites suggests a dry proto-Earth with subsequent delivery of volatiles by local accretion or impacts of asteroids or comets. Previous measurements in six comets from the Oort cloud yielded a mean D/H ratio of (2.96?±?0.25)?×?10(-4). The D/H value in carbonaceous chondrites, (1.4?±?0.1)?×?10(-4), together with dynamical simulations, led to models in which asteroids were the main source of Earth's water, with ≤10 per cent being delivered by comets. Here we report that the D/H ratio in the Jupiter-family comet 103P/Hartley 2, which originated in the Kuiper belt, is (1.61?±?0.24)?×?10(-4). This result substantially expands the reservoir of Earth ocean-like water to include some comets, and is consistent with the emerging picture of a complex dynamical evolution of the early Solar System.     

Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein.

N-linked glycosylation of proteins in eukaryotic cells follows a highly conserved pathway. The tetradecasaccharide substrate (Glc3Man9GlcNAc2) is first assembled at the membrane of the endoplasmic reticulum (ER) as a dolichylpyrophosphate (Dol-PP)-linked intermediate, and then transferred to nascent polypeptide chains in the lumen of the ER. The assembly of the oligosaccharide starts on the cytoplasmic side of the ER membrane with the synthesis of a Man5GlcNAc2-PP-Dol intermediate. This lipid-linked intermediate is then translocated across the membrane so that the oligosaccharides face the lumen of the ER, where the biosynthesis of Glc3Man9GlcNAc2-PP-Dol continues to completion. The fully assembled oligosaccharide is transferred to selected asparagine residues of target proteins. The transmembrane movement of lipid-linked Man5GlcNAc2 oligosaccharide is of fundamental importance in this biosynthetic pathway, and similar processes involving phospholipids and glycolipids are essential in all types of cells. The process is predicted to be catalysed by proteins, termed flippases, which to date have remained elusive. Here we provide evidence that yeast RFT1 encodes an evolutionarily conserved protein required for the translocation of Man5GlcNAc2-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER membrane.     

Fullerenes from aromatic precursors by surface-catalysed cyclodehydrogenation

Graphite vaporization provides an uncontrolled yet efficient means of producing fullerene molecules. However, some fullerene derivatives or unusual fullerene species might only be accessible through rational and controlled synthesis methods. Recently, such an approach has been used to produce isolable amounts of the fullerene C(60) from commercially available starting materials. But the overall process required 11 steps to generate a suitable polycyclic aromatic precursor molecule, which was then dehydrogenated in the gas phase with a yield of only about one per cent. Here we report the formation of C(60) and the triazafullerene C(57)N(3) from aromatic precursors using a highly efficient surface-catalysed cyclodehydrogenation process. We find that after deposition onto a platinum (111) surface and heating to 750 K, the precursors are transformed into the corresponding fullerene and triazafullerene molecules with about 100 per cent yield. We expect that this approach will allow the production of a range of other fullerenes and heterofullerenes, once suitable precursors are available. Also, if the process is carried out in an atmosphere containing guest species, it might even allow the encapsulation of atoms or small molecules to form endohedral fullerenes.