The Native Copper- and Zinc- Binding Protein Metallothionein Blocks Copper-Mediated Aβ Aggregation and Toxicity in Rat Cortical Neurons

Background: A major pathological hallmark of AD is the deposition of insoluble extracellular b-amyloid (Ab) plaques. There are compelling data suggesting that Ab aggregation is catalysed by reaction with the metals zinc and copper. Methodology/Principal Findings: We now report that the major human-expressed metallothionein (MT) subtype, MT-2A, is capable of preventing the in vitro copper-mediated aggregation of Ab1–40 and Ab1–42. This action of MT-2A appears to involve a metal-swap between Zn 7MT-2A and Cu(II)-Ab, since neither Cu 10MT-2A or carboxymethylated MT-2A blocked Cu(II)-Ab aggregation. Furthermore, Zn7MT-2A blocked Cu(II)-Ab induced changes in ionic homeostasis and subsequent neurotoxicity of cultured cortical neurons. Conclusions/Significance: These results indicate that MTs of the type represented by MT-2A are capable of protecting against Ab aggregation and toxicity. Given the recent interest in metal-chelation therapies for AD that remove metal from Ab leaving a metal-free Ab that can readily bind metals again, we believe that MT-2A might represent a different therapeuti

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

FIELD OBSERVATION SITE FOR AIR-SEA INTERACTIONS IN TROPICAL CYCLONES

Accurate predictions of winds, waves and currents within extreme tropical cyclones are critical for shipping, offshore oil and gas, ports and harbours, coastal erosion, tourism and fishing. The paper will describe a unique field observation programme intended to gather in situ data about air-sea interactions in tropical cyclones. The site has been established on the Woodside-operated North Rankin Complex, an offshore gas production facility located off the north-west coast of Western Australia. The facility is multi-purpose. It will assist Woodside to manage platform operations during the cyclone season and to make advances in the estimate of extreme wave crest heights for platform loading while enabling academic researchers to measure air-sea interactions. Concurrent measurements are conducted in the atmospheric boundary layer, on the ocean surface and below the surface all the way to the bottom at 120 m depth. The measurements include fluxes of momentum and energy across the air-sea interface, spray production, directional wave spectra up to high wavenumbers, and will allow us to close the balance of the air-sea exchanges for the first time in extreme field conditions