Reversed flow of Atlantic deep water during the Last Glacial Maximum

The meridional overturning circulation (MOC) of the Atlantic Ocean is considered to be one of the most important components of the climate system. This is because its warm surface currents, such as the Gulf Stream, redistribute huge amounts of energy from tropical to high latitudes and influence regional weather and climate patterns, whereas its lower limb ventilates the deep ocean and affects the storage of carbon in the abyss, away from the atmosphere. Despite its significance for future climate, the operation of the MOC under contrasting climates of the past remains controversial. Nutrient-based proxies and recent model simulations indicate that during the Last Glacial Maximum the convective activity in the North Atlantic Ocean was much weaker than at present. In contrast, rate-sensitive radiogenic (231)Pa/(230)Th isotope ratios from the North Atlantic have been interpreted to indicate only minor changes in MOC strength. Here we show that the basin-scale abyssal circulation of the Atlantic Ocean was probably reversed during the Last Glacial Maximum and was dominated by northward water flow from the Southern Ocean. These conclusions are based on new high-resolution data from the South Atlantic Ocean that establish the basin-scale north to south gradient in (231)Pa/(230)Th, and thus the direction of the deep ocean circulation. Our findings are consistent with nutrient-based proxies and argue that further analysis of (231)Pa/(230)Th outside the North Atlantic basin will enhance our understanding of past ocean circulation, provided that spatial gradients are carefully considered. This broader perspective suggests that the modern pattern of the Atlantic MOC-with a prominent southerly flow of deep waters originating in the North Atlantic-arose only during the Holocene epoch.     

Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation

Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.     

Realization of the Cirac-Zoller controlled-NOT quantum gate

Quantum computers have the potential to perform certain computational tasks more efficiently than their classical counterparts. The Cirac-Zoller proposal for a scalable quantum computer is based on a string of trapped ions whose electronic states represent the quantum bits of information (or qubits). In this scheme, quantum logical gates involving any subset of ions are realized by coupling the ions through their collective quantized motion. The main experimental step towards realizing the scheme is to implement the controlled-NOT (CNOT) gate operation between two individual ions. The CNOT quantum logical gate corresponds to the XOR gate operation of classical logic that flips the state of a target bit conditioned on the state of a control bit. Here we implement a CNOT quantum gate according to the Cirac-Zoller proposal. In our experiment, two 40Ca+ ions are held in a linear Paul trap and are individually addressed using focused laser beams; the qubits are represented by superpositions of two long-lived electronic states. Our work relies on recently developed precise control of atomic phases and the application of composite pulse sequences adapted from nuclear magnetic resonance techniques.     

Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease.     

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.     

Communications: quantum teleportation across the Danube

Efficient long-distance quantum teleportation is crucial for quantum communication and quantum networking schemes. Here we describe the high-fidelity teleportation of photons over a distance of 600 metres across the River Danube in Vienna, with the optimal efficiency that can be achieved using linear optics. Our result is a step towards the implementation of a quantum repeater, which will enable pure entanglement to be shared between distant parties in a public environment and eventually on a worldwide scale.     

Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs

RNA interference (RNAi) holds considerable promise as a therapeutic approach to silence disease-causing genes, particularly those that encode so-called 'non-druggable' targets that are not amenable to conventional therapeutics such as small molecules, proteins, or monoclonal antibodies. The main obstacle to achieving in vivo gene silencing by RNAi technologies is delivery. Here we show that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice. Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. We also show that these siRNAs can silence human apoB in a transgenic mouse model. In our in vivo study, the mechanism of action for the siRNAs was proven to occur through RNAi-mediated mRNA degradation, and we determined that cleavage of the apoB mRNA occurred specifically at the predicted site. These findings demonstrate the therapeutic potential of siRNAs for the treatment of disease.     

A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express

The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted.