Delayed kinetics of poliovirus RNA synthesis in a human cell line with reduced levels of hnRNP C proteins.

The hnRNP C heterotetramer [(C1(3))C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to re-localize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis

A functional role for small-conductance calcium-activated potassium channels in sensory pathways including nociceptive processes

We investigated the role of small-conductance calcium-activated potassium (SK) and intermediate-conductance calcium-activated potassium channels in modulating sensory transmission from peripheral afferents into the rat spinal cord. Subunit-specific antibodies reveal high levels of SK3 immunoreactivity in laminas I, II, and III of the spinal cord. Among dorsal root ganglion neurons, both peripherin-positive (C-type) and peripherin-negative (A-type) cells show intense SK3 immunoreactivity. Furthermore, dorsal root-stimulated sensory responses recorded in vitro are inhibited when SK channel activity is increased with 1-ethyl-2-benzimidazolinone (1-EBIO). In vivo electrophysiological recordings show that neuronal responses to naturally evoked nociceptive and nonnociceptive stimuli increase after application of the selective SK channel blocker 8,14-diaza-1,7( 1,4)-diquinolinacyclotetradecaphanedium ditrifluoroacetate (UCL 1848), indicating that SK channels are normally active in moderating afferent input. Conversely, neuronal responses evoked by mechanical stimuli are inhibited when SK channel activity is increased with 1-EBIO. These effects are reversed by the subsequent application of UCL 1848. Our data demonstrate that SK channels have an important role in controlling sensory input into the spinal cord

Mechanistic studies on Zymogen-activator and adhesion proteins (ZAAPs) as thrombolytic drugs and bacterial virulence factors

Streptokinase (SK), expressed by Lancefield Group A, C and G β-haemolytic Streptococci and Staphylocoagulase (SCG), expressed by S. aureus, are bacterial virulence factors which belong to a family of proteins known as Zymogen-activator and adhesion proteins (ZAAPs). SK and SCG are responsible for the non-proteolytic activation of plasminogen and prothrombin, respectively. Understanding of SK activity is exclusively based on the Group C (GCS) S. equisimilis H46a SK, a ‘clot buster’ or thrombolytic used in the treatment of Myocardial Infarction (MI), which exhibits no fibrin specificity. SK is the most used thrombolytic worldwide. Here, detailed kinetic studies in purified assay systems explored the mechanistic variation between a recombinant H46a SK (rSK H46a) and a Group A Streptococcal SK (M1GAS), most typically isolated in invasive human infection. This work demonstrates a fibrin specific mechanism for M1GAS SK and proposes a kinetic model for M1GAS SK plasminogen activation, to compliment the “Trigger and Bullet” hypothesis for H46a SK by Bock and colleagues. This work has relevance to the use of SK variants, with enhanced fibrin specificity, for improvement of thrombolytic therapies. Cardiovascular diseases such as myocardial infaraction and ischaemic stroke are significant casues of mortality, particularly in the developing world. Access to Alteplase, an expensive recombinant tPA and the only licensed treatment for stroke, is limited and there is interest in the use of SK for this purpose. Furthermore, microbial resistance is an increasing health burden, as demonstrated by programs such as the Longitude prize. Exploring the mechanisms of bacterial virulence factors at the molecular level such as this could provide rationale for the development of much-needed new antimicrobial technologies.  Open Acces

Construction and purpose of effective field theories for frustrated magnetic order

This article reviews recent years' progress in the low temperature analysis of standard models of spin glass order such as the Sherrington-Kirkpatrick (SK) model. Applications to CdTe/CdMnTe layered systems and explanation of glassy antiferromagnetic order at lowest temperatures stimulated us to study in detail the beautifully complex physical effects of replica symmetry breaking (RSB).We discuss analytical ideas based on highly precise numerical data which lead to the construction of relatively simple effective field theories for the SK model and help to understand the mysterious features of its exact solution. The goal is to find construction principles for the theory of interplay between frustrated magnetic order and various relevant physical degrees of freedom. The emphasis in this article is on the role of Parisi's RSB, which surprisingly creates critical phenomena in the low temperature limit despite the absence of a standard phase transition.Comment: Published online in Physica Status Solidi C (June 4 2007

Surface Diffusion and Islanding in Semiconductor Heterostructures

Molecular beam epitaxy (MBE) is an important technique for the creation of new, non-equilibrium semiconductor materials and structures exhibiting novel physical phenomena. Surface diffusion plays an important role in the growth of these structures, influencing such fundamental growth processes and constants as islanding, critical thickness and epitaxial temperatures. Two approaches to the general problem of surface diffusion and islanding, using the SiGe system as a prototypical semiconductor heterostructure, are discussed: The time evolution of patterned deposits, and kinetic studies of nucleation and growth. While disordered laminar growth occurs for deposition at 300 K, elevated temperatures lead to Stranski-Krastanow (SK) growth (uniform coverage SK with excess Ge in islands). Diffusion coefficients for Ge on Si(100) have been determined for coverages below SK and show a significant coverage dependence. They are extremely sensitive to contamination with carbon on the order of ≈0.05 ML, as well as to e-beam irradiation. In situ annealing experiments were performed to study the islanding process in real time. Provided the initial coverage exceeds the thickness of the SK layer, SK ≈3 ML on Si(100)2x1, the initially uniform but disordered layer begins to collapse into a SK-type morphology at about 250 °C. At a ramping rate of 0.1 °C/s this process is completed at ≈400 °C. A temperature dependence of the SK-layer thickness has been discovered for the first time. It is in excellent agreement with theoretical predictions

Design and manufacture of a novel system to simulate the biomechanics of basic and pitching shoulder motion

13openopenEntezari, V; Trechsel, BL; Dow, WA; Stanton, SK; Rosso, C; Müller, AM; McKenzie, B; Vartanians, V; CEREATTI, Andrea; DELLA CROCE, Ugo; Ramappa, J; De Angelis, JP; Nazarian, A.Entezari, V; Trechsel, Bl; Dow, Wa; Stanton, Sk; Rosso, C; Müller, Am; Mckenzie, B; Vartanians, V; Cereatti, Andrea; DELLA CROCE, Ugo; Ramappa, J; De Angelis, Jp; Nazarian, A