A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.

Hereditary hemochromatosis (HH) is a very common disorder characterized by iron overload and multi-organ damage. Several genes involved in iron metabolism have been implicated in the pathology of HH (refs. 1-4). We report that a mutation in the gene encoding Solute Carrier family 11, member A3 (SLC11A3), also known as ferroportin, is associated with autosomal dominant hemochromatosis.     

Forecasting market impact costs and identifying expensive trades

Often, a relatively small group of trades causes the major part of the trading costs on an investment portfolio. Consequently, reducing the trading costs of comparatively few expensive trades would already result in substantial savings on total trading costs. Since trading costs depend to some extent on steering variables, investors can try to lower trading costs by carefully controlling these factors. As a first step in this direction, this paper focuses on the identification of expensive trades before actual trading takes place. However, forecasting market impact costs appears notoriously difficult and traditional methods fail. Therefore, we propose two alternative methods to form expectations about future trading costs. Applied to the equity trades of the world's second largest pension fund, both methods succeed in filtering out a considerable number of trades with high trading costs and substantially outperform no‐skill prediction methods. Copyright © 2008 John Wiley & Sons, Ltd.     

On the Role of the Michelson–Morley Experiment: Einstein in Chicago

This article discusses new material, published in volume 12 of the Collected Papers of Albert Einstein, that addresses Einstein’s knowledge of the Michelson–Morley experiment prior to 1905: in a lecture in Chicago in 1921, Einstein referred to the experiment, mentioned when he came upon it and hinted at its influence. Arguments are presented to explain the contrast with Einstein’s later pronouncements on the role of the experiment.     

Water balance of global aquifers revealed by groundwater footprint

Groundwater is a life-sustaining resource that supplies water to billions of people, plays a central part in irrigated agriculture and influences the health of many ecosystems. Most assessments of global water resources have focused on surface water, but unsustainable depletion of groundwater has recently been documented on both regional and global scales. It remains unclear how the rate of global groundwater depletion compares to the rate of natural renewal and the supply needed to support ecosystems. Here we define the groundwater footprint (the area required to sustain groundwater use and groundwater-dependent ecosystem services) and show that humans are overexploiting groundwater in many large aquifers that are critical to agriculture, especially in Asia and North America. We estimate that the size of the global groundwater footprint is currently about 3.5 times the actual area of aquifers and that about 1.7 billion people live in areas where groundwater resources and/or groundwater-dependent ecosystems are under threat. That said, 80 per cent of aquifers have a groundwater footprint that is less than their area, meaning that the net global value is driven by a few heavily overexploited aquifers. The groundwater footprint is the first tool suitable for consistently evaluating the use, renewal and ecosystem requirements of groundwater at an aquifer scale. It can be combined with the water footprint and virtual water calculations, and be used to assess the potential for increasing agricultural yields with renewable groundwaterref. The method could be modified to evaluate other resources with renewal rates that are slow and spatially heterogeneous, such as fisheries, forestry or soil.     

Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.     

Recovery rates reflect distance to a tipping point in a living system

Tipping points, at which complex systems can shift abruptly from one state to another, are notoriously difficult to predict. Theory proposes that early warning signals may be based on the phenomenon that recovery rates from small perturbations should tend to zero when approaching a tipping point; however, evidence that this happens in living systems is lacking. Here we test such 'critical slowing down' using a microcosm in which photo-inhibition drives a cyanobacterial population to a classical tipping point when a critical light level is exceeded. We show that over a large range of conditions, recovery from small perturbations becomes slower as the system comes closer to the critical point. In addition, autocorrelation in the subtle fluctuations of the system's state rose towards the tipping point, supporting the idea that this metric can be used as an indirect indicator of slowing down. Although stochasticity prohibits prediction of the timing of critical transitions, our results suggest that indicators of slowing down may be used to rank complex systems on a broad scale from resilient to fragile.     

Spin-orbital separation in the quasi-one-dimensional Mott insulator Sr2CuO3

When viewed as an elementary particle, the electron has spin and charge. When binding to the atomic nucleus, it also acquires an angular momentum quantum number corresponding to the quantized atomic orbital it occupies. Even if electrons in solids form bands and delocalize from the nuclei, in Mott insulators they retain their three fundamental quantum numbers: spin, charge and orbital. The hallmark of one-dimensional physics is a breaking up of the elementary electron into its separate degrees of freedom. The separation of the electron into independent quasi-particles that carry either spin (spinons) or charge (holons) was first observed fifteen years ago. Here we report observation of the separation of the orbital degree of freedom (orbiton) using resonant inelastic X-ray scattering on the one-dimensional Mott insulator Sr2CuO3. We resolve an orbiton separating itself from spinons and propagating through the lattice as a distinct quasi-particle with a substantial dispersion in energy over momentum, of about 0.2 electronvolts, over nearly one Brillouin zone.     

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5?years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.     

Quantum supercurrent transistors in carbon nanotubes

Electronic transport through nanostructures is greatly affected by the presence of superconducting leads. If the interface between the nanostructure and the superconductors is sufficiently transparent, a dissipationless current (supercurrent) can flow through the device owing to the Josephson effect. A Josephson coupling, as measured by the zero-resistance supercurrent, has been obtained using tunnel barriers, superconducting constrictions, normal metals and semiconductors. The coupling mechanisms vary from tunnelling to Andreev reflection. The latter process has hitherto been observed only in normal-type systems with a continuous density of electronic states. Here we investigate a supercurrent flowing through a discrete density of states-that is, the quantized single particle energy states of a quantum dot, or 'artificial atom', placed between superconducting electrodes. For this purpose, we exploit the quantum properties of finite-sized carbon nanotubes. By means of a gate electrode, successive discrete energy states are tuned on- and off-resonance with the Fermi energy in the superconducting leads, resulting in a periodic modulation of the critical current and a non-trivial correlation between the conductance in the normal state and the supercurrent. We find, in good agreement with existing theory, that the product of the critical current and the normal state resistance becomes an oscillating function, in contrast to being constant as in previously explored regimes.