Evidence for neuromelanin involvement in MPTP-induced neurotoxicity

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduces certain clinical, pathological, and neurochemical features of Parkinson's disease. MPTP is metabolized by monoamine oxidase Type B to 1-methyl-4-phenylpyridine (MPP+), which is selectively accumulated by high-affinity uptake mechanisms into dopaminergic neurons. Lyden et al. described low-affinity binding of MPTP to synthetic and retinal melanin. We showed that MPP+ binds to neuromelanin with high affinity, suggesting that in MPTP neurotoxicity, MPP+ enters nigral neurons by the dopamine uptake system and binds to neuromelanin, which serves as a depot, continuously releasing MPP+ until it destroys the cells. This model predicts that agents which compete with MPP+ binding to neuromelanin should partially protect the dopamine neurons from MPTP-induced toxicity. The most potent identified competitor for MPP+ binding to melanin is the antimalarial drug chloroquine, which has a high affinity for melanins. In the present study, chloroquine, administered to monkeys in conventional anti-malarial doses before MPTP, protects them from MPTP-induced parkinsonian motor abnormalities, dopamine depletion in the striatum, and neuropathological changes in the substantia nigra.     

Superconductivity in lithium below 0.4 millikelvin at ambient pressure

Elements in the alkali metal series are regarded as unlikely superconductors because of their monovalent character. A superconducting transition temperature as high as 20 K, recently found in compressed lithium (the lightest alkali element), probably arises from pressure-induced changes in the conduction-electron band structure. Superconductivity at ambient pressure in lithium has hitherto remained unresolved, both theoretically and experimentally. Here we demonstrate that lithium is a superconductor at ambient pressure with a transition temperature of 0.4 mK. As lithium has a particularly simple conduction electron system, it represents an important case for any attempts to classify superconductors and transition temperatures, especially to determine if any non-magnetic configuration can exclude superconductivity down to zero temperature. Furthermore, the combination of extremely weak superconductivity and relatively strong nuclear magnetism in lithium would clearly lead to mutual competition between these two ordering phenomena under suitably prepared conditions.     

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.     

Pulsational pair instability as an explanation for the most luminous supernovae

The extremely luminous supernova SN 2006gy (ref. 1) challenges the traditional view that the collapse of a stellar core is the only mechanism by which a massive star makes a supernova, because it seems too luminous by more than a factor of ten. Here we report that the brightest supernovae in the modern Universe arise from collisions between shells of matter ejected by massive stars that undergo an interior instability arising from the production of electron-positron pairs. This 'pair instability' leads to explosive burning that is insufficient to unbind the star, but ejects many solar masses of the envelope. After the first explosion, the remaining core contracts and searches for a stable burning state. When the next explosion occurs, several solar masses of material are again ejected, which collide with the earlier ejecta. This collision can radiate 10(50) erg of light, about a factor of ten more than an ordinary supernova. Our model is in good agreement with the observed light curve for SN 2006gy and also shows that some massive stars can produce more than one supernova-like outburst.     

Hadean diamonds in zircon from Jack Hills, Western Australia

Detrital zircons more than 4 billion years old from the Jack Hills metasedimentary belt, Yilgarn craton, Western Australia, are the oldest identified fragments of the Earth's crust and are unique in preserving information on the earliest evolution of the Earth. Inclusions of quartz, K-feldspar and monazite in the zircons, in combination with an enrichment of light rare-earth elements and an estimated low zircon crystallization temperature, have previously been used as evidence for early recycling of continental crust, leading to the production of granitic melts in the Hadean era. Here we present the discovery of microdiamond inclusions in Jack Hills zircons with an age range from 3,058 +/- 7 to 4,252 +/- 7 million years. These include the oldest known diamonds found in terrestrial rocks, and introduce a new dimension to the debate on the origin of these zircons and the evolution of the early Earth. The spread of ages indicates that either conditions required for diamond formation were repeated several times during early Earth history or that there was significant recycling of ancient diamond. Mineralogical features of the Jack Hills diamonds-such as their occurrence in zircon, their association with graphite and their Raman spectroscopic characteristics-resemble those of diamonds formed during ultrahigh-pressure metamorphism and, unless conditions on the early Earth were unique, imply a relatively thick continental lithosphere and crust-mantle interaction at least 4,250 million years ago.     

Freiberg and the Frontier: Louis Janin,German Engineering,and ‘Civilisation’ in the American West

Mining companies after the Gold Rush depended heavily on foreign expertise, and yet historians of mining have glorified ‘German engineering’ in America. The application of German technology in America was fraught with difficulties, and most advances were micro- rather than macro-innovations, such as Philip Deidesheimer's famous square-set timbering on the Comstock Lode. The problem began at German mining schools, such as the Freiberg Mining Academy, where Americans like Louis and Henry Janin, while they acquired advanced training and adopted an engineering ethos, struggled to learn about Mexican and American mining. Having complemented their course of study to remedy this deficiency, the brothers returned to the US intending to modernize mining on the frontier. Louis attempted the ‘Freiberg Process’ of amalgamation on the Comstock Lode, but locally developed methods proved more feasible, and the experiment failed. He came to apply his training rather toward the micro-level problem of how to reprocess amalgamation waste heaps.