The component polypeptide chains of bovine insulin nucleate or inhibit aggregation of the parent protein in a conformation-dependent manner

Amyloid fibrils are typically rigid, unbrariched structures with diameters of similar to 10 nm and lengths up to several micrometres, and are associated with more than 20 diseases including Alzheimer's disease and type II diabetes. Insulin is a small, predominantly alpha-helical protein consisting of 51 residues in two disulfide-linked polypeptide chains that readily assembles into amyloid fibrils under conditions of low PH and elevated temperature. We demonstrate here that both the A-chain and the B-chain of insulin are capable of forming amyloid fibrils in isolation under similar conditions, with fibrillar morphologies that differ from those composed of intact insulin. Both the A-chain and B-chain fibrils were found to be able to cross-seed the fibrillization of the parent protein, although these reactions were substantially less efficient than self-seeding with fibrils composed of full-length insulin. In both cases, the cross-seeded fibrils were morphologically distinct from the seeding, material, but shared common characteristics with typical insulin fibrils, including a very similar helical repeat. The broader distribution of heights of the cross-seeded fibrils compared to typical insulin fibrils, however, indicates that their underling protofilament hierarchy may be subtly different. In addition, and remarkably in view of this seeding behavior, the soluble forms of the A-chain and B-chain peptides were found to be capable of inhibiting insulin fibril formation. Studies using mass spectrometry suggest that this behavior might be attributable to complex formation between insulin and the A-chain and B-chain peptides. The finding that the same chemical form of a polypeptide chain in different physical states can either stimulate or inhibit the conversion of a protein into amyloid fibrils sheds new light on the mechanisms underlying fibril formation, fibril strain propagation and amyloid disease initiation and progression. (c) 2006 Elsevier Ltd. All rights reserved.

Large inert carbon pool in the terrestrial biosphere at the Last Glacial Maximum

During each of the late Pleistocene glacial–interglacial transitions, atmospheric carbon dioxide concentrations rose by almost 100 ppm. The sources of this carbon are unclear, and efforts to identify them are hampered by uncertainties in the magnitude of carbon reservoirs and fluxes under glacial conditions. Here we use oxygen isotope measurements from air trapped in ice cores and ocean carbon-cycle modelling to estimate terrestrial and oceanic gross primary productivity during the Last Glacial Maximum. We find that the rate of gross terrestrial primary production during the Last Glacial Maximum was about 40±10 Pg C yr−1, half that of the pre-industrial Holocene. Despite the low levels of photosynthesis, we estimate that the late glacial terrestrial biosphere contained only 330 Pg less carbon than pre-industrial levels. We infer that the area covered by carbon-rich but unproductive biomes such as tundra and cold steppes was significantly larger during the Last Glacial Maximum, consistent with palaeoecological data. Our data also indicate the presence of an inert carbon pool of 2,300 Pg C, about 700 Pg larger than the inert carbon locked in permafrost today. We suggest that the disappearance of this carbon pool at the end of the Last Glacial Maximum may have contributed to the deglacial rise in atmospheric carbon dioxide concentrations.

Processes driving intraseasonal displacements of the eastern edge of the warm pool: the contribution of westerly wind events

We investigate the processes responsible for the intraseasonal displacements of the eastern edge of the western Pacific warm pool (WPEE), which appear to play a role in the onset and development of El Niño events. We use 25 years of output from an ocean general circulation model experiment that is able to accurately capture the observed displacements of the WPEE, sea level anomalies, and upper ocean zonal currents at intraseasonal time scales in the western and central Pacific Ocean. Our results confirm that WPEE displacements driven by westerly wind events (WWEs) are largely controlled by zonal advection. This paper has also two novel findings: first, the zonal current anomalies responsible for the WPEE advection are driven primarily by local wind stress anomalies and not by intraseasonal wind-forced Kelvin waves as has been shown in most previous studies. Second, we find that intraseasonal WPEE fluctuations that are not related to WWEs are generally caused by intraseasonal variations in net heat flux, in contrast to interannual WPEE displacements that are largely driven by zonal advection. This study hence raises an interesting question: can surface heat flux-induced zonal WPEE motions contribute to El Niño–Southern Oscillation evolution, as WWEs have been shown to be able to do?