Genome stability, progressive kidney failure and aging

Two new studies report mutations in FAN1 and three other genome-stability genes that tie the DNA damage response to progressive kidney failure and the dysfunction of several other organs. These findings provide clues to the underlying causes of tissue decline and may add a series of genes to the growing list of genome maintenance factors that protect against premature aging.     

Metallurgy: high nickel release from 1- and 2-euro coins

The amount of nickel is regulated in European products that come into direct and prolonged contact with human skin because this metal may cause contact allergy, particularly hand eczema. Here we show that 1- and 2-euro coins induce positive skin-test reactions in sensitized individuals and release 240-320-fold more nickel than is allowed under the European Union Nickel Directive. A factor contributing to this high release of nickel is corrosion due to the bimetallic structure of these coins, which generates a galvanic potential of 30-40 mV in human sweat.     

An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division

RNA interference (RNAi) is an evolutionarily conserved defence mechanism whereby genes are specifically silenced through degradation of messenger RNAs; this process is mediated by homologous double-stranded (ds)RNA molecules. In invertebrates, long dsRNAs have been used for genome-wide screens and have provided insights into gene functions. Because long dsRNA triggers a nonspecific interferon response in many vertebrates, short interfering (si)RNA or short hairpin (sh)RNAs must be used for these organisms to ensure specific gene silencing. Here we report the generation of a genome-scale library of endoribonuclease-prepared short interfering (esi)RNAs from a sequence-verified complementary DNA collection representing 15,497 human genes. We used 5,305 esiRNAs from this library to screen for genes required for cell division in HeLa cells. Using a primary high-throughput cell viability screen followed by a secondary high content videomicroscopy assay, we identified 37 genes required for cell division. These include several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Thus, our study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells.     

SLAC1 is required for plant guard cell S-type anion channel function in stomatal signalling

Stomatal pores, formed by two surrounding guard cells in the epidermis of plant leaves, allow influx of atmospheric carbon dioxide in exchange for transpirational water loss. Stomata also restrict the entry of ozone--an important air pollutant that has an increasingly negative impact on crop yields, and thus global carbon fixation and climate change. The aperture of stomatal pores is regulated by the transport of osmotically active ions and metabolites across guard cell membranes. Despite the vital role of guard cells in controlling plant water loss, ozone sensitivity and CO2 supply, the genes encoding some of the main regulators of stomatal movements remain unknown. It has been proposed that guard cell anion channels function as important regulators of stomatal closure and are essential in mediating stomatal responses to physiological and stress stimuli. However, the genes encoding membrane proteins that mediate guard cell anion efflux have not yet been identified. Here we report the mapping and characterization of an ozone-sensitive Arabidopsis thaliana mutant, slac1. We show that SLAC1 (SLOW ANION CHANNEL-ASSOCIATED 1) is preferentially expressed in guard cells and encodes a distant homologue of fungal and bacterial dicarboxylate/malic acid transport proteins. The plasma membrane protein SLAC1 is essential for stomatal closure in response to CO2, abscisic acid, ozone, light/dark transitions, humidity change, calcium ions, hydrogen peroxide and nitric oxide. Mutations in SLAC1 impair slow (S-type) anion channel currents that are activated by cytosolic Ca2+ and abscisic acid, but do not affect rapid (R-type) anion channel currents or Ca2+ channel function. A low homology of SLAC1 to bacterial and fungal organic acid transport proteins, and the permeability of S-type anion channels to malate suggest a vital role for SLAC1 in the function of S-type anion channels.     

Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4

Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.     

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.     

Decoherence-protected quantum gates for a hybrid solid-state spin register

Protecting the dynamics of coupled quantum systems from decoherence by the environment is a key challenge for solid-state quantum information processing. An idle quantum bit (qubit) can be efficiently insulated from the outside world by dynamical decoupling, as has recently been demonstrated for individual solid-state qubits. However, protecting qubit coherence during a multi-qubit gate is a non-trivial problem: in general, the decoupling disrupts the interqubit dynamics and hence conflicts with gate operation. This problem is particularly salient for hybrid systems, in which different types of qubit evolve and decohere at very different rates. Here we present the integration of dynamical decoupling into quantum gates for a standard hybrid system, the electron-nuclear spin register. Our design harnesses the internal resonance in the coupled-spin system to resolve the conflict between gate operation and decoupling. We experimentally demonstrate these gates using a two-qubit register in diamond operating at room temperature. Quantum tomography reveals that the qubits involved in the gate operation are protected as accurately as idle qubits. We also perform Grover's quantum search algorithm, and achieve fidelities of more than 90% even though the algorithm run-time exceeds the electron spin dephasing time by two orders of magnitude. Our results directly allow decoherence-protected interface gates between different types of solid-state qubit. Ultimately, quantum gates with integrated decoupling may reach the accuracy threshold for fault-tolerant quantum information processing with solid-state devices.     

论焓的物理意义

尽管焓在自然科学、工程热物理和热能工程中是使用十分广泛的物理参量,但其物理意义却是不够清楚的。本文首先评价了已有的一些关于焓的物理意义的论点,然后论述并发挥了作者以前论述过的焓中的pv是在压力场为定常时,流体微团在其迹线上的压力势能的观点。为此,需涉及到体系的势能与外力场对体系作功的关系,以及流体微元体在流场中运动时,流场对此微元体的作功关系的定量概念。通过以上论述,以期对探讨焓的物理意义有所帮助。     

Charge self-regulation upon changing the oxidation state of transition metals in insulators

Transition-metal atoms embedded in an ionic or semiconducting crystal can exist in various oxidation states that have distinct signatures in X-ray photoemission spectroscopy and 'ionic radii' which vary with the oxidation state of the atom. These oxidation states are often tacitly associated with a physical ionization of the transition-metal atoms--that is, a literal transfer of charge to or from the atoms. Physical models have been founded on this charge-transfer paradigm, but first-principles quantum mechanical calculations show only negligible changes in the local transition-metal charge as the oxidation state is altered. Here we explain this peculiar tendency of transition-metal atoms to maintain a constant local charge under external perturbations in terms of an inherent, homeostasis-like negative feedback. We show that signatures of oxidation states and multivalence--such as X-ray photoemission core-level shifts, ionic radii and variations in local magnetization--that have often been interpreted as literal charge transfer are instead a consequence of the negative-feedback charge regulation.     

Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis

Endocytosis is a key cellular process, encompassing different entry routes and endocytic compartments. To what extent endocytosis is subjected to high-order regulation by the cellular signalling machinery remains unclear. Using high-throughput RNA interference and automated image analysis, we explored the function of human kinases in two principal types of endocytosis: clathrin- and caveolae/raft-mediated endocytosis. We monitored this through infection of vesicular stomatitis virus, simian virus 40 and transferrin trafficking, and also through cell proliferation and apoptosis assays. Here we show that a high number of kinases are involved in endocytosis, and that each endocytic route is regulated by a specific kinase subset. Notably, one group of kinases exerted opposite effects on the two endocytic routes, suggesting coordinate regulation. Our analysis demonstrates that signalling functions such as those controlling cell adhesion, growth and proliferation, are built into the machinery of endocytosis to a much higher degree than previously recognized.