Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B) has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD) of NS4B is highly conserved in Hepaciviruses, though its function remains unknown.</p> <p>Results</p> <p>A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH). The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD) of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system.</p> <p>Conclusion</p> <p>Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.</p

Electrical detection of 31P spin quantum states

In recent years, a variety of solid-state qubits has been realized, including quantum dots, superconducting tunnel junctions and point defects. Due to its potential compatibility with existing microelectronics, the proposal by Kane based on phosphorus donors in Si has also been pursued intensively. A key issue of this concept is the readout of the P quantum state. While electrical measurements of magnetic resonance have been performed on single spins, the statistical nature of these experiments based on random telegraph noise measurements has impeded the readout of single spin states. In this letter, we demonstrate the measurement of the spin state of P donor electrons in silicon and the observation of Rabi flops by purely electric means, accomplished by coherent manipulation of spin-dependent charge carrier recombination between the P donor and paramagnetic localized states at the Si/SiO2 interface via pulsed electrically detected magnetic resonance. The electron spin information is shown to be coupled through the hyperfine interaction with the P nucleus, which demonstrates the feasibility of a recombination-based readout of nuclear spins

Charge Induced Vortex Lattice Instability

It has been predicted that superconducting vortices should be electrically charged and that this effect is particularly enhanced for, high temperature superconductors.\cite{kho95,bla96} Hall effect\cite{hag91} and nuclear magnetic resonance (NMR) experiments\cite{kum01} suggest the existence of vortex charging, but the effects are small and the interpretation controversial. Here we show that the Abrikosov vortex lattice, characteristic of the mixed state of superconductors, will become unstable at sufficiently high magnetic field if there is charge trapped on the vortex core. Our NMR measurements of the magnetic fields generated by vortices in Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+y}$ single crystals\cite{che07} provide evidence for an electrostatically driven vortex lattice reconstruction with the magnitude of charge on each vortex pancake of $\mathbf{\sim 2}$x$\mathbf{10^{-3} e}$, depending on doping, in line with theoretical estimates.\cite{kho95,kna05}Comment: to appear in Nature Physics; 6 pages, 7 figure

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (&lt;100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Wilson-loop formalism for Reggeon exchange in soft high-energy scattering

We derive a nonperturbative expression for the non-vacuum, qqbar-Reggeon-exchange contribution to the meson-meson elastic scattering amplitude at high energy and low momentum transfer, in the framework of QCD. Describing the mesons in terms of colourless qqbar dipoles, the problem is reduced to the two-fermion-exchange contribution to the dipole-dipole scattering amplitudes, which is expressed as a path integral, over the trajectories of the exchanged fermions, of the expectation value of a certain Wilson loop. We also show how the resulting expression can be reconstructed from a corresponding quantity in the Euclidean theory, by means of analytic continuation. Finally, we make contact with previous work on Reggeon exchange in the gauge/gravity duality approach.Comment: A few misprints in the expressions for the relevant Wilson loops have been corrected. 55 pages, 7 figure

Generalized quark-antiquark potential at weak and strong coupling

We study a two-parameter family of Wilson loop operators in N=4 supersymmetric Yang-Mills theory which interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines. These observables capture a natural generalization of the quark-antiquark potential. We calculate these loops on the gauge theory side to second order in perturbation theory and in a semiclassical expansion in string theory to one-loop order. The resulting determinants are given in integral form and can be evaluated numerically for general values of the parameters or analytically in a systematic expansion around the 1/2 BPS configuration. We comment about the feasibility of deriving all-loop results for these Wilson loops.Comment: 43 pages: 15 comprising the main text and 25 for detailed appendice

Nonperturbative contributions to the quark form factor at high energy

The analysis of nonperturbative effects in high energy asymptotics of the electomagnetic quark form factor is presented. It is shown that the nonperturbative effects determine the initial value for the perturbative evolution of the quark form factor and find their general structure with respect to the high energy asymptotics. Within the Wilson integral formalism which is natural for investigation of the soft, IR sensitive, part of the factorized form factor, the structure of the instanton induced effects in the evolution equation is discussed. It is demonstrated that the instanton contributions result in the finite renormalization of the subleading perturbative result and numerically are characterized by small factor reflecting the diluteness of the QCD vacuum within the instanton liquid model. The relevance of the IR renormalon induced effects in high energy asymptotic behaviour is discussed. The consequences of the various analytization procedures of the strong coupling constant in the IR domain are considered.Comment: REVTeX, 12 pages, 1 figure. Important references and discussions added, misprints corrected, minor changes in tex

Estimated pre-morbid IQ effects on cognitive and functional outcomes in Alzheimer disease: a longitudinal study in a treated cohort

Abstract Background Cognitive reserve is thought to influence the degree of neuropathology needed for diagnosis of Alzheimer disease (AD). Cognitive reserve can be operationally defined as the hypothesized capacity of the mature adult brain to sustain the effects of disease or injury without manifesting clinical symptoms of AD, but sufficient to cause clinical dementia in an individual possessing less cognitive reserve. Its effect on the subsequent course of AD is less clear. Pre-morbid IQ is a useful measure of cognitive reserve. Methods We studied 659 consecutive patients with AD at a tertiary referral memory clinic. Patients were assessed on six cognitive tests at baseline. Activities of Daily Living (ADL) were measured on the Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). The National Adult Reading Test (NART) was used to estimate pre-morbid IQ. Patients were followed up after starting a cholinesterase inhibitor over 78 weeks. Mixed general linear models estimated the effects of NART on cognition and ADL. Results Three hundred and fifty-five patients had NART scored with a mean estimated pre-morbid IQ of 104.7 (standard deviation 18.5). NART increased overall cognitive ability by 2.7% for every 10 IQ points (p Conclusion Our data support the hypothesis that cognitive reserve continues to have a limited influence on cognition after AD has been diagnosed and thus, indirectly, has an impact on ADL.</p

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children