Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions

An incubatable direct current stimulation system for in vitro studies of Mammalian cells.

The purpose of this study was to provide a simplified alternative technology and format for direct current stimulation of mammalian cells. An incubatable reusable stimulator was developed that effectively delivers a regulated current and does not require constant monitoring

Marginal states of the resistive tearing mode with flow in cylindrical geometry

The linear stability of tearing modes in a cylindrical plasma subject to a sub-Alfvénic equilibrium shear flow along the equilibrium magnetic field is considered. The equations in the resistive boundary layer at the rational surface are solved numerically using a Fourier transform combined with a finite-element approach. The behaviour of the growth rate as a function of the flow and the various parameters (including a perpendicular fluid viscosity) is obtained. Marginal stability curves showing the dependence of the familiar matching parameter Δ' with flow and shear are also given

Exciton Dynamics in Carbon Nanotubes: From the Luttinger Liquid to Harmonic Oscillators

We show that the absorption spectrum in semiconducting nanotubes can be determined using the bosonization technique combined with mean-field theory and a harmonic approximation. Our results indicate that a multiple band semiconducting nanotube reduces to a system of weakly coupled harmonic oscillators. Additionally, the quasiparticle nature of the electron and hole that comprise an optical exciton emerges naturally from the bosonized model.Comment: 5 pages, 3 figure

Gamma rays of 0.3 to 30 MeV from PSR 0531+21

Pulsed gamma rays from the Crab Pulsar PSR 0531+21 are reported for energies of 0.3 to 30 MeV. The observations were carried out with the UCR gamma ray double Compton scatter telescope launched on a balloon from Palestine, Texas at 4.5 GV, at 2200 LT, September 29, 1978. Two 8 hr observations of the pulsar were made, the first starting at 0700 UT (0200 LT) September 30 just after reaching float altitude of 4.5 g/sq cm. Analysis of the total gamma ray flux from the Crab Nebula plus pulsar using telescope vertical cell pairs was published previously. The results presented supersede the preliminary ones. The double scatter mode of the UCR telescope measures the energy of each incident gamma ray from 1 to 30 MeV and its incident angle to a ring on the sky. The time of arrival is measured to 0.05 ms. The direction of the source is obtained from overlapping rings on the sky. The count rate of the first scatter above a threshold of 0.3 MeV is recorded every 5.12 ms. The Crab Pulsar parameters were determined from six topocentric arrival times of optical pulses

Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits.

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation

'I Sat Filling in This Form While Smoking and It Was Divine'. An Analysis of Free-Text Comments from Smokers Who Report They Have No Intention of Quitting in the Next Six Months

INTRODUCTION: Smokers unmotivated to quit are neglected by smoking cessation research. Free-text comment analysis is a potentially useful way to gain insight into this group's beliefs. AIMS: To analyse the free-text comments provided by smokers unmotivated to quit as part of a randomized controlled trial of computer-tailored feedback for smoking cessation. METHOD: A random sample of 58,660 smokers were sent a smoking behaviour questionnaire (SBQ). The responses and follow-up outcomes of those providing free-text comments were compared to those who did not to assess the representativeness of the former group of smokers. The comments of participants unmotivated to quit (631) were thematically analysed. RESULTS: Those who provided a comment differed from those who did not on variables including education level and quit attempts at six-month follow-up. Emergent themes included; justification of smoking and restricting smoking instead of quitting. CONCLUSIONS: The findings illustrate the value of free-text comments in identifying issues important to respondents. The identified themes highlight areas for future research in smokers unmotivated to quit including cutting down as a path to quitting and explicit messages regarding the inability of positive health behaviours to balance out the negative impact of smoking on health. Trial registration: Current Controlled Trials ISRCTN05385712