Respiratory syncytial virus NS1 protein degrades STAT2 by using the elongin-cullin E3 ligase

Respiratory syncytial virus (RSV) infection causes bronchiolitis and pneumonia in infants. RSV has a linear single-stranded RNA genome encoding 11 proteins, 2 of which are nonstructural (NS1 and NS2). RSV specifically downregulates STAT2 protein expression, thus enabling the virus to evade the host type I interferon response. Degradation of STAT2 requires proteasomal activity and is dependent on the expression of RSV NS1 and NS2 (NS1/2). Here we investigate whether RSV NS proteins can assemble ubiquitin ligase (E3) enzymes to target STAT2 to the proteasome. We demonstrate that NS1 contains elongin C and cullin 2 binding consensus sequences and can interact with elongin C and cullin 2 in vitro; therefore, NS1 has the potential to act as an E3 ligase. By knocking down expression of specific endogenous E3 ligase components using small interfering RNA, NS1/2, or RSV-induced STAT2, degradation is prevented. These results indicate that E3 ligase activity is crucial for the ability of RSV to degrade STAT2. These data may provide the basis for therapeutic intervention against RSV and/or logically designed live attenuated RSV vaccines.

Inflammation markers are associated with Cardiovascular diseases risk in adolescents The Young Hearts Project 2000

Purose: The traditional approach for identifying subjects at risk from cardiovascular diseases (CVD) is to determine the extent of clustering of biological risk factors adjusted for lifestyle. Recently, markers of endothelial dysfunction and low grade inflammation, including high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecules (sICAM), and soluble vascular adhesion molecules (sVCAM), have been included in the detection for high risk individuals. However, the relationship of these novel biomarkers with CVD risk in adolescents remains unclear. The purpose of this study, therefore, was to establish the association of hsCRP, sICAM, and sVCAM with CVD risk in an adolescent population.
Methods: Data from the Young Hearts 2000 cross-sectional cohort study, carried out in 1999-2001, were used. From a total of 2,017 male and female participants, 95 obese subjects were identified and matched according to age, sex, and cigarette smoking, with 95 overweight and 95 normal-weight adolescents. Clustered CVD risk was computed using a sum of Z-scores of biological risk factors. The relationship was described using multiple linear regression analyses.
Results: hsCRP, sICAM, and sVCAM showed significant associations with CVD risk. hsCRP and sICAM had a positive relation with CVD risk, whereas sVCAM showed an inverse relationship. In this study, lifestyle factors showed no relation with CVD risk.
Conclusion: The results fit the hypothesized role of low grade inflammation and endothelial dysfunction in CVD risk in asymptomatic adolescents. The inverse relationship of VCAM, however, is hard to explain and indicates the complex mechanisms underlying CVD. Further research is needed to draw firm conclusions on the biomarkers used.

Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD.

Micronutrients: dietary intake v. supplement use

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and beta-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.

Entanglement detection in hybrid optomechanical systems

We study a device formed by a Bose-Einstein condensate (BEC) coupled to the field of a cavity with a moving end mirror and find a working point such that the mirror-light entanglement is reproduced by the BEC-light quantum correlations. This provides an experimentally viable tool for inferring mirror-light entanglement with only a limited set of assumptions. We prove the existence of tripartite entanglement in the hybrid device, persisting up to temperatures of a few milli-Kelvin, and discuss a scheme to detect it.

Physical model for the generation of ideal resources in multipartite quantum networking

We propose a physical model for generating multipartite entangled states of spin-s particles that have important applications in distributed quantum information processing. Our protocol is based on a process where mobile spins induce the interaction among remote scattering centers. As such, a major advantage lies in the management of stationary and well-separated spins. Among the generable states, there is a class of N-qubit singlets allowing for optimal quantum telecloning in a scalable and controllable way. We also show how to prepare Aharonov, W, and Greenberger-Horne-Zeilinger states.

A geometric analysis of the effects of noise on Berry phase

In this work we describe the effect of classical and quantum noise on the Berry phase. It is not a topical review article but rather an overview of our work in this field aiming at giving a simple pictorial intuition of our results.

Berry phase in open quantum systems: a quantum Langevin equation approach

The evolution of a two level system with a slowly varying Hamiltonian, modeled as a spin 1/2 in a slowly varying magnetic field, and interacting with a quantum environment, modeled as a bath of harmonic oscillators is analyzed using a quantum Langevin approach. This allows to easily obtain the dissipation time and the correction to the Berry phase in the case of an adiabatic cyclic evolution.

A scheme for entanglement extraction from a solid

Some thermodynamical properties of solids, such as heat capacity and magnetic susceptibility, have recently been shown to be linked to the amount of entanglement in a solid. However, this entanglement may appear a mere mathematical artefact of the typical symmetrization procedure of many-body wavefunction in solid state physics. Here we show that this entanglement is physical, demonstrating the principles of its extraction from a typical solid-state system by scattering two particles off the system. Moreover, we show how to simulate this process using present day optical lattice technology. This demonstrates not only that entanglement exists in solids but also that it can be used for quantum information processing or as a test of Bell's inequalities.

Cloning transformations in spin networks without external control

In this paper we present an approach to quantum cloning with unmodulated spin networks. The cloner is realized by a proper design of the network and a choice of the coupling between the qubits. We show that in the case of phase covariant cloner the XY coupling gives the best results. In the 1 -> 2 cloning we find that the value for the fidelity of the optimal cloner is achieved, and values comparable to the optimal ones in the general N -> M case can be attained. If a suitable set of network symmetries are satisfied, the output fidelity of the clones does not depend on the specific choice of the graph. We show that spin network cloning is robust against the presence of static imperfections. Moreover, in the presence of noise, it outperforms the conventional approach. In this case the fidelity exceeds the corresponding value obtained by quantum gates even for a very small amount of noise. Furthermore, we show how to use this method to clone qutrits and qudits. By means of the Heisenberg coupling it is also possible to implement the universal cloner although in this case the fidelity is 10% off that of the optimal cloner.

Quantum cloning in spin networks

We introduce an approach to quantum cloning based on spin networks and we demonstrate that phase covariant cloning can be realized using no external control but only with a proper design of the Hamiltonian of the system. In the 1-->2 cloning we find that the XY model saturates the value for the fidelity of the optimal cloner and gives values comparable to it in the general N-->M case. We finally discuss the effect of external noise. Our protocol is much more robust to decoherence than a conventional procedure based on quantum gates.

Entanglement production by quantum error correction in the presence of correlated environment

We analyze the effect of a quantum error correcting code on the entanglement of encoded logical qubits in the presence of a dephasing interaction with a correlated environment. Such correlated reservoir introduces entanglement between physical qubits. We show that for short times the quantum error correction interprets such entanglement as errors and suppresses it. However, for longer time, although quantum error correction is no longer able to correct errors, it enhances the rate of entanglement production due to the interaction with the environment.